Bis (3 3-dichloro-2-oxo-polymethyleneimines)

ABSTRACT

THE INVENTION RELATES TO 3,3 - DICHLORO-2-OXOPOLYMETHYLENIMINES AND BIS(3,3 - DICHLORO - 2-OXOPOLYMETHYLENIMINES) HAVING USEFUL ANTI-INFLAMMATORY PROPERTIES AS DETERMINED BY THEIR INHIBITION OF CARRAGEENAN INDUCED EDEMA IN RATS.

United States Patent 3,647,782 BIS (3,3-DICHLORO-Z-OXO-POLYMETHYLENE- IMINES Joseph C. Collins, East Greenbush, N.Y., assignor to Sterling Drug Inc., New York, NY.

No Drawing. Continuation-impart of application Ser. No. 673,926, Oct. 9, 1967. This application Sept. 29, 1969, Ser. No. 862,084

Claims priority, application Great Britain, Oct. 1, 1968,

46,633/ 68 Int. Cl. C07d 41/06 US. Cl. 260-239.3 R 8 Claims ABSTRACT OF THE DISCLOSURE The invention relates to 3,3 dichloro-Z-oxopolymethylenimines and bis(3,3 dichloro 2-oxopolymethylenimines) having useful anti-inflammatory properties as determined by their inhibition of carrageenan induced edema in rats.

The application is a continuation-in-part of prior copending application, Ser. No. 673,926, filed Oct. 9, 1967, now US. Pat. 3,549,654 issued Dec. 22, 1970.

This invention relates to 3,3-dichloro-2-oxopolymethylenimine derivatives and bis(3,3 dichloro 2-oxopolymethylenimine) derivatives.

Accordng to one aspect of the invention there is provided the compounds having the Formula I c1 01 l R where -R is one of the group consisting of phenyl-loweralkyl, 3-indolyl-lower-alkyl, phenyal, naphthyl, 5,657,8- tetrahydronaphthyl, fluorenyl, 9-oxofluorenyl, pyridyl, pyrimidinyl and benzothiazolyl radicals, and such radicals substituted by from one to three substituents of the group consisting of halo, lower-alkyl, phenyl-lower-alkyl, lower-alkoxy, phenyl-lower-alkoxy, phenoxy, lower-alkylmercapto, lower-alkylsulfonyl, trihalomethyl, nitro, di

,(lower-alkyl)amino. lower-alkanoylamino, amino, lower- 3,647,782 Patented Mar. 7, 1972 wuere NB is one of the group consisting of l-pyrrolidinyl, 1-piperidinyl, 4 lower-alkyl-l-piperazinyl, 4-benzyl-1 piperazinyl, 4-phenyl-1-piperazinyl, 4-morpholinyl and 4- thiomorpholinyl, or NB is NR'R where R and R, which can be the same or different, are lower-alkyl, benzyl, phenyl, or phenyl substituted by from one to three substituents of the group consisting of halo, lower-alkyl, lower-a1koxy, trihalomethyl and nitro; and n is a number from 1 to 3 inclusive.

In the compound of Formula II above, when phenyl is substituted, as described above, by more than one substituent, such substituents can be the same or different and they can be in any of the various position combinations relative to each other.

According to another aspect of the invention there is provided the compounds having the Formula III III where Ar is phenylene, biphenylylene, or phenylene or biphenylylene substituted by from one to three substituents of the group consisting of halo, lower-alkyl, phenyl lower-alkyl, lower-alkoxy, phenyl-lower-alkoxy, phenoxy, lower-alkylmercapto, lower-alkylsulfonyl, trihalomethyl, nitro, di(lower alkyl)amino, lower alkanoylamino, amino, lower alkanoyloxy, and hydroxy; m is a number from 0 to 3 inclusive; and m is a number from 1 to 3 inclusive.

In the compounds of the invention having the Formula III above, when phenylene or biphenylylene, represented by Ar, are substituted, as described hereinabove, by more than one substituent, such substituents can be the same or different and they can be in any of the various position combinations relative to each other.

According to another aspect of the invention there is provided the compounds having the Formula IV where Y is alkylene having from two to twelve carbon atoms, and n is a number from 1 to 3 inclusive.

In Formula I above where R is phenyl-lower-alkyl or phenyl-lower-alkyl substituted as hereinbettore defined for the radicals represented by R, the term phenyllower-alky means a group wherein lower-alkyl contains from one to six carbon atoms which can be arranged as straight or branched chains, which without limiting the ClI2HCI'I2CHZCH3, CH2(BHCH2CI{2CH2CH3 CH CH(CH )CH(CH )CH CH CH and the like.

The term halo, as used hereinabove and throughout this specification, includes chloro, bromo, iodo and fiuoro.

The terms lower-alkyl, lower-alkanoyloxy, loweralkanoyl, and lower-alkoxy, as used hereinabove and be F as Straight branched i wh with throughout this specification, mean such groups prefer- Out hrintmg the generahtypf the foregomg Illustrated ably containing from one to six carbon atoms which by (3'mdyl)m ethy1 f' can be arranged as straight or branched chains, and withand the b out limiting the generality of the foregoing, are illustrated The drvalent aromatic radicals ash represented y A1 by methyl, ethyl, propyl, isopropyl, butyl, secbmyl amyl in Formula III can have ea ih of t err two connecting hexyl, acetoxy, propionoxy trimethylacetoxy, acetyl, prof hnkage? to any aval able carbon atom of the pionyl, trimethylacetyl, methoxy, ethoxy, isobutoxy, and aromatic rings such that they can be in any of the various the mm Posmon combmatlons lrelatlve to h other The novel compounds of the invention, represented In the above F when 1S the nitrogen by Formulas I, II, III and IV above, are prepared by atoms a each hnked dlrecfly to a mug Carbon atom of cyclization of the corresponding w-chloroalkanoic acid the radlcals represented by amides having the Formulas VA and VB, (ii-chloro- In f Formula Whem m 18 a number 10m alkanoic acid hydrazides having the Formulas VIA and to 3 mcluslve CmHZm represents lower'alkylene as VIB, and bis(w-chloroalkanoic acid amides) havingthe Illustrated by CH2 CH2CHZ*" CH2CH2CH2*" Formulas IXA and IXB and the Formulas XIA and X13 "CH(CH3)CHZ and further reacting the resulting cyclized compounds of i I I Formulas VIlB, VIIIB, XB, and XIIB with a chlorinat- CHCH -CH(C2H5), and -CH --Gl-ICH ing agent so as to dichlorinate the ring carbon atom vicinal to each ring carbonyl group. In Formula IV above, Y represents alkylene havmg O 0 its connecting linkages on different carbon atoms as g 01 illustrated by CH CH CH CH CH NQ 2)4-, 2)5 2)6 2)s' 01 O NH Q .i l G1 I OH CH -01 2)1o 2)12, 3) 2 Z VHMQZR) C(CH3) 2CH2 VIA (Q:NB) VIIIA (Q=NB) 9 2 CH2 NHQ c (gil chlorination (Q=R) Formula I 9 .(CH2)5CH2C1 (CH2 n tion (Q NB) VB (Q=R) VIIB (Q=R) ula II VIB (aqua) VIIIB (Q=NB) o o 11 a 6 3'1 c -c NH-(C H )-Ar-(C H )-NH -Cl .2 RC1 CH -CH Cl cln o-cfi IXA O 0 cl II I If CZLU- (c n Ar-(C H )-N: :l c1

2 m 2m m 2m 2 -2 H61 (CH CH C1 0lH C-(CH 9 l (sig -ca es. ma e-(011 -2 HCl XIB XIIB where R, NB, Ar, m and n, and Y have the meaning hereinbefore defined for R of Formula I; NB of Formula II; Ar, rm and n of Formula III; and Y of Formula IV respectively, except that the radicals represented by R and Ar cannot bear amino and/or hydroxy substituents, such substituents being introduced as described hereinbelow,

The cyclization reaction is advantageously performed in a suitable solvent in the presence of at least a stoichiometric amount of an acid-acceptor and in a temperature range of from about 5 C. to 80 C.

The cyclization of the w-chloroalkanoic acid amides of Formula VA and Formula VB where n is a number from 1 to 2 inclusive, the w-chloroalkanoic acid hydrazides of Formula VIA and Formula VIB where n is a number from 1 to 2 inclusive and the biS(m-Chl.0- alkanoic acid amides) of Formulas IXA and XIA and Formulas IXB and XIB where n is a number from 1 to 2 inclusive is preferably carried out at room temperature in methyl or ethyl alcohol in the presence of a stoichiometric amount of slight excess of sodium hydroxide.

The cyclization of the w-chloroalkanoic acid amides of Formula VB where n is the number 3 and the w-ChlOIO- alkanoic acid hydrazides of Formula VIB, where n is the number 3 and the bis(w-chloroalkanoic acid amides) of Formulas D03 and XIB, where n is the number 3, is preferably carried out in dimethyl sulfoxide in the presence of a stoichiometric amount or slight excess of potassium tert-butoxide at a temperature of from about C. to 80 C.

The compounds of Formula VIIB, Formula VIIIB, Formula XB and Formula XIIB can be converted to the corresponding compounds of Formula 1, Formula II, Formula HI and Formula IV respectively by reaction in a suitable solvent, e.g., xylene, benzene or chloroform, with a suitable chlorinating agent, e.g., chlorine gas in the presence of either phosphorus trichloride or phosphorus pentachloride; sulfuryl chloride in the presence of phosphorus pentachloride; or phosphorus pentachloride Depending on the chlorinating agent and solvent used the reaction temperature can range from about 15 to 120 C. and the reaction time can range from about onehalf hour to about twenty-four hours. The preferred reaction is carried out with at least one equivalent of phosphorus pentachloride. The reaction is conveniently carried out by suspending three to four equivalents of phosphorus pentachloride in a suitable solvent, adding a solution of the appropriate 2-oxocyclomethylenimine or bis(2-oxo- 'f l l o 0 G1 I! II C 1 elm-rm: Tc;

chlorination Formula IV cyclomethylenimine) in a suitable solvent and finally heating in the range of about 50 to about 100 C. The following general procedure illustrates the preferred method:

A solution of the appropriate 2-oxocyclomethylenimine derivative (0.10 mole) or bis(2-oxocyclomethylenimine) (0.10 mole) in 150 ml. xylene is added dropwise during one hour to a stirred suspension of three equivalents of phosphorus pentachloride in 200 ml. xylene at room temperature. The mixture is heated during one hour to to C. and heating is continued for one-half hour. The mixture is evaporated to dryness under reduced pressure and the residue is stirred with excess aqueous sodium carbonate solution. The reulting insoluble material is collected and recrystallized from a suitable solvent to give the corresponding 3,3-dichloro-2-oxopolymethylenimine derivative, or bis(3,3-dichloro-2-oxopolymethylenimine) respectively The intermediate w-chloroalkanoic acid amides having the Formula VA and VB, w-chloroalkanoic acid hydrazides VIA and VIB, and the bis(w-chloroalkanoic acid amides) having the Formulas DCA, IXB, XIA and XIB are prepared by reacting the corresponding amines having the Formula R-NH (XIII), hydrazines having the Formula H N-NB (XIV) and di-amines having the formulas -H N(C H2m)-Ar(C H )-NH (XV) and H N-Y-NH (XVI), where R, NB, Ar and m, and Y have the meaning hereinbefore defined for R of Formula VA; NB of Formula II; Ar and m of Formula IXA; and Y of Formula IV respectively, which belong to known classes of compounds with the appropriate amount of the known acid chloride, 2,2,4-trichlorobutyryl chloride, or the known acid chloride having the formula ClCH (CH CH COCl (XVII), where rt is the number from 1 to 3 inclusive, that is, 4-chlorobutyryl chloride, S-chlorovaleryl chloride and 6-chlorohexanoyl chloride, in a suitable solvent in the presence of at least a stoichiometric amount of an acid-acceptor such as sodium hydroxide, sodium carbonate, or triethylamine and at a temperature range from about 0 to 25 C.

The reaction is preferably carried out by dissolving an appropriate amine having the Formula XIII, hydrazine having the Formula XIV, or di-amine having the Formulas XV or XVI, in benzene, methylene dichloride or ethylene dichloride, adding an excess of triethylamine or a stoichiometric amount of aqueous sodium carbonate or sodium hydroxide, cooling to 5 to 10 C., and gradually adding a stoichiometric amount or slight excess of the appropriate acid chloride.

The compounds of Formula I where the radicals represented by R are substituted by one or more amino and/ or hydroxy substituents, and the compounds of Formula III where Ar is substituted by one or more amino and/ or hydroxy substituents are prepared, by well known hydrolysis procedures, from the corresponding compounds where the radicals represented by R and Ar are substituted by one or more lower-alkanoylamino and/or lower-alkanoyloxy substituents, whereby said substituents are converted to amino and/or hydroxy substituents.

In the case of a lower-alkanoylamino substituent, e.g. an acetamido substituent, the hydrolysis can be carried out at room temperature in ether containing an amount of hydrogen chloride slightly in excess of one equivalent. The amine hydrochloride salt so obtained can be converted to the corresponding free base by neutralization with an equivalent of a suitable acid acceptor.

In the case of a lower-alkanoyloxy substituent, e.g. acetoxy substituent, the hydrolysis can be carried out at room temperature in aqueous methyl alcohol containing an amount of potassium hydroxide slightly in excess of one equivalent.

The hydrazines having the Formula XIV are known componds or are readily prepared from well known, readily available amines having the Formula XVIII (H--NB) by standard procedures, e.g. by nitrosation followed by reduction of the N-nitroso intermediate so obtained.

The following general procedure exemplifies the method:

To a vigorously stirred solution of one mole of amine (H-NB, XVIII) in 145 ml. concentrated hydrochloric acid and 400 g. ice-water is added a solution of one mole sodium nitrite in 250 ml. water during ten minutes, while the reaction temperature is maintained below C. and stirring is continued one hour. The reaction mixture is extracted with a suitable solvent, e.g. benzene and the extract is evaporated to dryness under reduced pressure. The crude N-nitroso compound (ONNB, XIX) can be purified if desired by well known procedures, e.g. by distillation under reduced pressure or recrystallization. To a vigorously stirred mixture of 4.3 g-atoms of zinc dust in 400 ml. water is added slowly a solution of one mole of the N-nitroso compound in 4.8 moles glacial acetic acid during two hours while the reaction temperature is maintained at 10 to 20 C. Stirring is continued for one hour and the mixture then is warmed to about 80 C. and filtered. The cooled filtrate is treated with an amount of 40% aqueous sodium hydroxide sufficient to redissolve the precipitated zinc hydroxide and then extracted with a suitable solvent, e.g. ether. The extract is evaporated to dryness and the crude product is purified by well known procedures to give the hydrazine of Formula XIV (H NNB).

The compounds of the invention, having the Formulas I, II, III and IV above, are therapeutically active substances which possess useful anti-inflammatory properties. The actual determination of the numerical biological data definitive for a particular compound is readily determined by standard test procedures by technicians having ordinary skill in pharmacological test procedures, without the need for any extensive experimentation.

The anti-inflammatory activity of the compounds of the invention having the Formulas I, II, III and IV above, was determined in the carrageenan edema test [Winter et al., Proc. Soc. Exp. Biol. Med. 111, 544-547 (1962)] wherein the test agents were administered orally in multiple doses to fasted male albino rats. One hour after medication five hundredths of one ml. of 0.75% carrageenan was injected into the foot of each rat and three hours after the injections of carrageenan the weight of the foot edema was determined. The calculated difference between the average weight of the control and medicated rats was used as a measure of the degree of inhibition of carrageenan edema due to the administration of the test agent. Consistent, significant inhibition of carrageenan edema was foundwhen the compounds of acacia, and the like) for oral administration.

The molecular structures of the compounds of the invention were assigned on the basis of the method of their synthesis and study of their infrared spectra, and confirmed by the correspondence between calculated and found values for the elementary analysis for representative examples.

The invention is illustrated by the following examples:

Example 1.-Method 1 (A) N-(4-chlorophenyl)-2,2,4-trichlorobutyramide To a stirred, ice-cooled mixture of 4.2 g. sodium hydroxide in ml. water and 12.7 g. 4-chloroaniline in 200 ml. ethylene dichloride was added 21 g. 2,2,4-trichlorobutyryl chloride during fifteen minutes. The mixture was stirred for one-half hour and the precipitate was filtered and Washed with water. The filtrate was washed with dilute aqueous hydrochloric acid solution and water, dried over sodium sulfate, and evaporated to dryness to yield N-(4-chlorophenyl)-2,2,4-trichlorobutyramide as a solid which was combined with the crop obtained by filtration and used as such in the next step.

(B) 3 ,3-dichloro-1-(4-chlorophenyl)-2-pyrrolidinone To a stirred solution of the N-(4-chlorophenyl)-2,2,4- trichlorobutyramide, from Example 1A, in 200 ml. ethyl alcohol was added a solution of 4.2 g. sodium hydroxide in 42 ml. water. Stirring was continued for ten minutes and dilute aqueous hydrochloric acid solution was added until the solution turned acidic, followed by 300 ml. water. The resulting crystals were filtered to give after recrystallization from carbon tetrachloride 18.4 g. 3,3- dichloro-1-(4-chlorophenyl)-2-pyrrolidinone; M.P. r1084- 109.2 C. (corr.).

METHOD 2 (A) N- (4-chlorophenyl) -4-chlorobutyramide To a stirred, ice cooled mixture of 25.5 g. of 4-chloroaniline and 25.3 g. triethylamine in 800 ml. dry methylene dichloride was added a solution of 31 g. 4-chlorobutyryl chloride in 300 ml. dry methylene dichloride dropwise during one hour. The resulting solution was allowed to Warm to room temperature, washed with 5% aqueous sodium carbonate solution and water, dried over anhydrous calcium sulfate and evaporated to dryness under reduced pressure to give after successive recrystallizations from ethyl acetate-hexane and ethyl alcohol-hexane 17.9 g. N-(4-chlorophenyl)-4-chlorobutyramide; M.P. 100- 101 'C.

(B) 1- (4-chlorophenyl Z-pyrrolidinone To a stirred solution of 11.6 g. 'N-(4-chlorophenyl)-4- chlorobutyramide in 75 ml. ethyl alcohol was added 5 ml. of a solution of 0.5 g. sodium hydroxide in water and three additional identical sodium hydroxide solutions were added at ten, twenty and forty minute intervals. The solution was allowed to stand for fifteen hours, diluted with 25 ml. water and the resulting crystals werecollected by filtration to give after recrystallization from ethyl alcohol-hexane 5.9 g. l-(4-chlorophenyl)-2-pyrrolidinone; M.P. 96.5-97.5 C. i

To a stirred slurry of 15.6 phosphorus pentachloride in 65 ml. xylene was added a solution of 4.9 g. Il-(4-chlorophenyl)-2-pyrrolidinone in 40 ml. xylene dropwise during five minutes and the resulting mixture was slowly heated to 80 C. during twenty minutes and heating at '80" C. was continued for forty-five minutes. The solvent was removed under reduced pressure at about 75 C. and the residual viscous oil was stirred with 55 ml. 10% aqueous sodium carbonate and ice. The resulting solid was collected by filtration and washed with water to give after recrystallization from methyl alcohol-water 3.9 g. 3,3- dichloro-1-(4-chlorophenyl)-2-pyrrolidinone; M.P. 112- 113 C.

' EXAMPLE 2 (A) N- 2-chlorophenyl -2 ,2,4-trichlorobutyramide To a stirred, ice-cooled mixture of 9.5 g. 2-chloroaniline in 100 ml. ethylene dichloride and 3.15 g. sodium hydroxide in 75 ml. water was added 15.8 g. 2,2,4-trichlorobutyryl chloride in 50 mL'ethylene dichloride during one-halt hour and stirring was continued one-half hour. The ethylene dichloride phase was separated, washed with dilute aqueous hydrochloric acid and water and evaporated to dryness to yield N-(2-ch1orophenyl)- 2,2,4-trichlorobutyramide as a yellow oil which was used as such in the next step.

(B 3 ,3 -dichlor-1-(2-chlorophenyl) -2-pyrro1idinone (a) 4-(n-'butyl)aniline b) Z-bromo-4,6-dinitroaniline (c) 3,4-diethoxyaniline (d) 4-buty1mercaptoaniline (e) 2,4,5-trichloroaniline (f) 2-bromo-6-ch1oro-4-nitroaniline (g) 4-(j-phenylpentyloxy)aniline (h) 4-phenethyloxyaniline (i) Z-bromo-4-is0pentylaniline (j) 2,5-dimethyl-4-nitroaniline (k) 2-butoxyaniline 1 (l) 2,6-dichloro-4-ethylmercaptoaniline (m) 4-(tert-butyl)sulfonylaniline (n) 4- 3-(4-nitrophenyl propyl] aniline (o) 4-dimethylaminoaniline (p) 4-dibutylaminoaniline there can be obtained respectively, according to this invention:

(a) N-[4-(n-butyl)phenyl]-2,2,4-trichlorobutyramide ('b) N-(2-bromo-4,6 dinitrophenyl)-2,2,4-trichlorobutyramide e (c) N-(3,4-diethoxyphenyl)-2,2,4-trichlorobutyramide (d) N-(4-butylmercaptophenyl)-2,2,4-trichlorobutyramide (e) N 2,4,5 -trichlorophenyl -2,2,4-trichlorobutyramide (f) N-(2 bromo-6-chloro-4-nitrophenyl)-2,2,4-trichlorobutyramide r (g) N- [4- -phenylpentyloxy) phenyl] 2,2,4-trichlorobutyramide I (h) -N-(4-phenethyloxyphenyl)-2,2,4-trichlorobutyramide (i) N-(2-bromo-4-isopenty1phenyl)-2,2,4-trichlorobutyramide (j) N-(2,5-dimethyl-4-nitrophenyl)-2,2,4-trichlorobutyramide (k) N-(Z-butoxyphenyl)-2,2,4-trichlorobutyramide (1) N-(2,6-dichloro-4-ethylmercaptophenyl)-2,2,4-trichlorobutyramide (m) N-[4-(tert-butyl)sulfonylphenyl]-2,2,4-trichlorobutyramide (n) N-{4-[3-(4-nitropheny1)propyl]phenyl}-2,2,4-trichlorobutyramide (o) tN-(4-dimethylaminophenyl)-2,2,4-trichlorobutyramide (p) N- (4-dibutylaminophenyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and substituting for 2,2,4-trichlorobutyryl chloride an equivalent amount of 6-chlorohexanoyl chloride there can be obtained:

N- 2-chl0rophenyl) -6-chlorohexanamide Following a procedure similar to that described in Example 2B and substituting for N-(Z-chlorophenyl)-2,2,4- trichlorobutyramide and equivalent amount of:

(a) N- [4- (n-butyl) phenyl] -2,2,4-trichlorobutyramide (b) N-(2-bromo-4,6-dinitrophenyl)-2,2,4-trichlorobutyramide (c) N-(3,4-diethoxyphenyl)-2,2,4-trichlorobutyramide (d) N-(4-butylmercaptophenyl)-2,2,4-trichlorobutyramide (e) N- 2,4,5 -trichlorophenyl -2,2,4-trichlorobutyramide (f) N-(2-bromo-6-chloro-4-nitrophenyl)-2,2,4-trichlorobutyramide (g) N- [4- S-phenylpentyloxy)phenyl] -2,2,4-trichlorobutyramide (h) N-(4-phenethyloxyphenyl)-2,2,4-trichlorobutyramide (i) N-(2-bromo-4-isopentylphenyl)-2,2,4-trichlorobutyramide (j) N- (2,5 -dimethyl-4-nitrophenyl) -2,2,4-trichlorobutyramide (k) N-(2-butoxyphenyl)-2,2,4-trichlorobutyramide (l) (2,6-dichl0ro-4-ethylmercaptophenyl)-2,2,4-trichlor0- butyramide (m) N-[4-(tert-butyl)sulfonylphenyl]-2,2,4-trichlorobutyramide (n) N-{4- [3- (4-nitropheny1) propyl] phenyl}-2,2,4-trichlorobutyramide (o) N-(4-dimethylaminophenyl)-2,2,4-trichlorobutyramide (p) N-(4-dibutylaminophenyl)-2,2,4-trichlorobutyramide (q) N-(2-chlorophenyl)-6-chlorohexanamide there can be obtained respectively, according to this invention:

(a) 3,3-dichloro-1-[4-(n-butyl)pheny1]-2-pyrrolidinone (b) 3,3-dichloro-1-(2-bromo-4,6-dinitrophenyl)-2-pyrrolidinone (c) 3 ,3-dich1or0-1- 3,4-diethoxyphenyl) -2-pyrrolidinone (d) 3 ,3-dichloro-1- (4-butylmercapto-pheny1) -2-pyrrolidinone (e) 3,3-dichloro-1-(2,4,5-trichloropheny1) -2-pyrrolidinone (f) 3,3-dichloro-1- (2-bromo-6-chloro-4-nitropheny1) -2- pyrrolidinone (g) 3,3-dichloro-l-[4-(5-phenylpentyloxy)phenyl]-2- pyrrolidinone (h) 3,3-dich1oro-l- (4-phenethyloxyphenyl) -2-pyrrolidinone (i) 3,3-dichloro-1-(2-bromo-4-isopentylphenyl)-2-pyrrolidinone p (j) 3,3-dichloro-1-(2,5-dimethyl-4-nitrophenyl)-2-pyrrolidinone (k) 3, 3-dichlorol-(2-butoxyphenyl) -2-pyrrolidinone (l) 3,3-dichloro-1-(2,6-dichloro-4-ethylmercaptophenyl)- 2-pyrrolidinone (m) 3,3-dichloro-l- [4- (tert-butyl) sulfonylphenyl) ]-2- pyrrolidinone (n) 3,3-dichloro-1-{4-[3-(4-nitrophenyl)propyl] phenyl}-2-pyrrolidinone (o) 3,3-dichloro-1-(4-dimethylaminophenyl) -2-pyrrolidinone (p) 3,3-dichloro-l-(4-dibutylaminophenyl)-2-pyrrolidinone (q) 1- 2-chlorophenyl -hexahydro-2H-azepin-2-one Following the general procedure described hereinbefore for the chlorination of a 2-oxopolymethylenimine and using the following:

1- 2-chlorophenyl) -hexahydro-2H-azepin-2-one there can be obtained:

3,3-dichloro-l-(2-chloropheny1) -hexahydro-2H-azepin- 2-one Following a procedure similar to that described in Example 2A and substituting for 2-chloroaniline and sodium hydroxide an equivalent amount of 4-acetoxyaniline and triethylamine respectively and omitting the 75 ml. water, there can be obtained according to this invention N-(4- acetoxyphenyl)-2,2,4-trichlorobutyramide.

Following a procedure similar to that described in Example 2B and substituting for N-(2-chlorophenyl)-2,2,4 trichlorobutyrarnide an equivalent amount of N-(4-acetoxyphenyl)-2,2,4-trichlorobutyramide and increasing the amount of ethyl alcohol from 150 ml. to 300 ml., there can be obtained 3,3-dichloro-1-(4-acetoxypheny1)-2pyrrolidinone.

By treating 3,3-dich1oro-1-(4-acetoxyphenyl)-2-pyrrolidinone in aqueous methyl alcohol, at room temperature, with an amount of potassium hydroxide which is in slight excess of that required to hydrolyze the acetoxy group, there can be obtained 3,3-dichloro-1-(4-hydroxyphenyl -2-pyrrolidinone.

EXAMPLE 3 (A) N- 3 )-chlorophenyl -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 6.37 g. 3-chloroaniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-(3-chlorophenyl)-2,2,4-trichlorobutyramide as an orange oil which was used as such in the next step.

(B) 3,3-dichloro-1- 3-chlorophenyl) -2-pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(3-chlorophenyl)-2,2,4-trichlo robutyramide from Example 3A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol-water 6.7 g. 3,3-dichloro-1-(3-chlorophenyl)-2-pyrrolidinone; M.P. 76-775 C.

EXAMPLE 4 (A) N-(3-fluorophenyl) -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 5.55 g. 3-fiuoroaniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-(3 fluorophenyl)-2,2,4-trichlorobutyramide as an orange oil which was used as such in the next step.

(B) 3, 3-dichloro-1- (3-fluorophenyl) -2-pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(3-fiuorophenyl)-2,2,4-trichlorobutyramide from Example 4A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from benzene-hexane 7.3 g. 3,3-dichloro-1-(3-fluorophenyl)-2 pyrrolidinone; M.P. 8890 C.

EXAMPLE 5 N-(4-fluorophenyl) 2,2,4-trichlorobutyramide Following a procedure similar to that described in Example-2A and using 5.55 g. 4-fluoroaniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyryl chloride there was obtained N-(4-fluorophenyl)-2,2,4-trichlorobutyramide as brown crystals which was usedas such in the next step.

(B) 3,3-dichlorol- (4-fluorophenyl) -2-pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(4-fiuor0phenyl)-2,2,4-trichlorobutyramide from Example 5A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol-water 5.8 g. 3,3-dichloro-l-(4-fiuorophenyl)-2-pyrrolidinone; M.P. 106l07 C.

EXAMPLE 6 (A) N- 4-bromophenyl -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 8.6 g. 4-bromoaniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-( 4-bromophenyl)-2,2,4-trichlorobutyramide as a yellow oil which was used as such in the next step.

(B) 3,3-dichlorol-(4-bromophenyl) -2-pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(4-bromophenyl)-2,2,4-trichlorobutyramide from Example 6A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from benzene-hexane 9.8 g. 3,3-dichloro-l-(4-bromophenyl)-2- pyrrolidinone; M.P. 122-124 C.

EXAMPLE 7 (A) N-phenyl-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 4.65 g. aniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-phenyl-Z,2,4-trichlorobutyramide as a yellow solid which was used as such in the next step.

(B) 3,3-dichloro-1-phenyl-2-pyrrolidinone I Following a procedure similar to that described in Example 2B and using the N-phenyl-2,2,4-trichlorobutyramide from Example 7A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol-water 6.3 g. of 3,3-dichloro-l-phenyl-Z-pyrrolidinone; M.P. 87 C.

EXAMPLE 8 q I (A) N-(4-tolyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 5.35 g. p-toluidine, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-(4-tolyl)-2,2,4-trichlorobutyramide as an oil which was used as such in the next step.

(B) 3,3-dichloro l-(4-tolyl)-2-pyrrolidinone V p EXAMPLE 9 (A) N 4-methoxyphenyl -2,2,4-trichlo robutyramide Following a procedure similar to that described in Examp1e2A and using 6.15 g. p-anisidine, 2.1 g. sodium hydroxide and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-(4-methoxyphenyl)-2,2,4-trichloro- (B) 3,3-dichloro-1-(4-methoxyphenyl)-2 pyrrolidinone Following a-procedure similar to that described in Example 2B and using the N-(4-methoxyphenyl)-2,2,4- trichlorobutyramide from Example 9A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from ethyl acetate 5.9 g. 3,3-dichloro-1-(4-methoxyphenyl)-2- pyrrolidinone; M.P. 12l12l.5- C.

EXAMPLE 10 (A) N- (3,4-dimethoxyphenyl) -2,2,4-trich1orobutyramide Following a procedure similar to that described in Example 2A and using 7.2 g. 3,4-dimethoxyaniline, 2.0 g. sodium hydroxide, and 9.9 g. 2,2,4-trichlorobutyryl chloride, therew as obtained N-(3,4-dimethoxyphenyl)-2,2,4- trichlorobutyramide which was used without further purification in the next step.

(B) 3, 3-dichloro-1-(3,4-dimethoxyphenyl)-2- pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(3,4-dimethoxyphenyl)- 2,2,4-trichlorobutyramide from Example 10A and 2.0 g. sodium hydroxide, there was obtained after recrystallization from acetone 6.9 g. 3,3-dichloro-1-(3,4-dimethoxyphenyl)-2-pyrrolidinone; M.P. 183-185 C.

EXAMPLE 11 (A) N-(3-chloro-6-methoxyphenyl-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 7.87 g. 3-chloro-6-methoxyaniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trich1orobutyryl chloride, there was obtained N-(3-chloro-6-methoxyphenyl)-2,2,4-trichlorobutyramide as a brown oil which which was used as such in the next step.

(B) 3 ,3-dichloro-1- (3-chloro-6-methoxyphenyl) -2- pyrrolidinone EXAMPLE 12 (A) N-(4-benzyloxyphenyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 10 g. 4-benzyloxyaniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4trichlorobutyryl chloride, there was obtained N-(4-benzyloxyphenyl)-2,2,4-trichlorobutyramide as a solid which was used as such in the next step.

(B) 3,3-dichloro-1-(4-benzyloxyphenyl)-2- pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(4benzyloxyphenyl)-2,2,4- trichlorobutyramide from Example 12A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from benzene-hexane 9.5 g. 3,3-dichloro-1-(4-benzyloxyphenyl)-2-pyrrolidinone; M.P. 1 635-165" C.

EXAMPLE 13 (A) N-(4-acetamidophenyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 4.5 g. 4-acetamidoaniline, 1.3 g. sodium hydroxide, and 6.3 g. 2,2,4,-trichlorobutyryl chloride, there was obtained N-(4-acetamidophenyl)-2,2,4-trichlorobutyramide as a solid which was used as such in the next step.

(B) 3,3-dichloro-1-(4-acetamidopheny1)-2-pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(4-acetamidophenyl)-2,2,4- triohlorobutyramide from Example 13A and 1.3 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol 4.1 g. '3,3-dichloro-1-(4-acetamidophenyl)-2-pyrrolidinone; M.P. -196 C. (dec.).

By treating 3,3-dichloro-1-(4-acetamidophenyl)-2-pyrrolidinone in absolute ethyl alcohol, at room temperature, with an ethereal solution containing an amount of hydrogen chloride slightly in excess of that required to hydrolyze the acetamido group, there can be obtained the hydrochloride salt of 3,3-dichloro-1-(4-aminophenyl)-2-pyrrolidinone which can be converted to the free base by dissolving the salt in ethyl alcohol and treating the resulting solution with an equivalent amount of sodium carbonate in water.

EXAMPLE 14 (A) N-(4-nitrophenyl) -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 6.9 g. 4-nitroaniline, 4.4 g. sodium bicarbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-(4-nitrophenyl)-2,2,4-trichlorobutyramide as yellow crystals which were used as such in the next step.

(B 3 3-dichloro-1- (4-nitrophenyl) -2-pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-(4-nitrophenyl)-2,2,4-trichlorobutyramide from Example 14A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from acetone-water 6.0 g. 3,3-dichloro-1- (4-nitrophenyl)-2-pyrr01- idinone; M.P. 162l63 C.

EXAMPLE 15 (A) N- [4- trifluoromethyl phenyl] -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 8.05 g. 4-(trifluoromethy1)aniline, 4.4 g. sodium bicarbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-[4-(trifiuoromethyl) phenyl]-2,2,4-trichlorobutyramide as yellow crystals which was used as such in the next step.

(B) 3,3-dichloro-1-[4-(trifluoromethyl)phenyl]- 2-pyrrolidinone Following a procedure similar to that described in Example 2B and using the N-[4-(trifluoromethyl)phenyl]- 2,2,4-trichlorobutyramide from Example 15A and 2.1 g. sodium hydroxide there was obtained after recrystallization from methyl alcohol 6.4 g. 3,3-dichloro-1-[4-trifluoromethyl)pheny1]-2-pyrrolidinone; M.P. 106-107 C.

EXAMPLE 16 (A) N-[2-(triiiuoromethyl)phenyl]-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 2A and using 8.05 g. (2-trifluoromethyl)aniline, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyry1 chloride, there was obtained N-[2-(trifluoromethyl)phenyl]-2,2,4-trichlorobutyramide as a yellow oil which was used as such in the next step.

(B) 3,3-dichloro-1- [Z-trifiuoromethyl) phenyl] 2-pyrrolidinone A procedure was followed similar to that described in Example 2B, using the N- [2-(trifluoromethyl)phenyl]- 2,2,4-trichlorobutyramide from Example 16A and 2.1 g. sodium hydroxide, except that the reaction solution was diluted with water and extracted with benzene. Evaporation of the benzene extract to dryness yielded, after recrys- 15 tallization from hexane, 4.0 g. 3,3-dichloro-1-[trifluoromethyl)phenyl]-2-pyrrolidinone; M.P. 64.5 C.

. EXAMPLE 17 (A) N- (Z-naphthyl) -2,2,4-trichlorobutyramide To a stirred ice-cooled mixture of 7.16 g. Z-naphthylamine in 150 ml. benzene and 5.63 g. sodium carbonate in water was added 10.5 g. 2,2,4-trichlorobutyryl chloride in 50 ml. benzene during one-half hour and stirring was continued one-half hour with cooling and one and one-half hours at room temperature. The benzene phase was separated, washed with dilute aqueous hydrochloric acid solution, water, dilute sodium bicarbonate solution and water, dried over calcium sulfate and evaporated to dryness to yield 15.9 g. (N-(Z-naphthyl)-2,2,4-trichlorobutyramide as a solid which was used as such in the next step.

(B) 3 ,3-dichloro-1-(2-naphthy1) -2-pyrrolidinone To the N-(2-naphthyl)-2,2,4-trichlorobutyramide from Example 17A in 100 ml. ethyl alcohol was added, with stirring, a solution of 1.0 g. sodium hydroxide in 10 ml. water and when the pH of the reaction mixture returned to approximately seven an additional solution of 1.0 g. of sodium hydroxide in 10 ml. water was added. When the pH of the reaction mixture returned to approximately seven, it was adjusted to pH thirteen by the addition of 50% aqueous sodium hydroxide solution and stirring was continued for one hour. The reaction mixture was diluted with water and the resulting precipitate was collected by (filtration and recrystallized from methyl alcohol to yield 11.0 g. 3,3-dichloro-I-(Z-naphthyl)-2-pyrrolidinone; M.P. 163.5-164.5 C.

EXAMPLE 18 (A) N- (4-chlorol-naphthyl -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 17A and using 8.88 g. 4-chloro-1-aminonaphthalene, 5.62 g. sodium carbonate and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained 16.6 g. N-(4-chlorol-naphthyl)-2,2,4-trichlorobutyramide which was used as such in the next step.

(B) 3,3-dichloro-1- (4-chloro-1-naphthyl) -2-pyrrolidinone Following a procedure similar to that described in Example 17B and using 16.6 g. N-(4-chl0ro-1-naphthyl)- 2,2,4-trichlorobutyramide from Example 18A and 1.48 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol 11.9 g. 3,3-dichloro-l-(4-chloro-l-naphthyl)-2-pyrrolidinone; M.P. 211.9-220 C.

EXAMPLE 19 (A) N- l-naphthyl) -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 17A and using 7.15 g. l-naphthylamine, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyry1 chloride, there was obtained N-(l-naphthyl)-2,2,4-trichlrobutyramide as a brown gum which was used as such in the next step.

(B) 3,3-dichloro-1-( 1-naphthyl) -2-pyrrolidinone Following a procedure similar to that described in Example 17B and using the N-(1-naphthyl)-2,2,4-trichlorobutyramide from Example 19A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol 9.05 g. 3,3-dichloro-1-(1-naphthyl)2- pyrrolidinone; M.P. 150151 C.

Following a procedure similar to that described in Example 17A and substituting for Z-naphthylamine an equivalent amount of:

.(a) 1-amino-2-bromo-4,7-dinitronaphthalene (b) 1-amino-2-methoxy-6-methylsulfonylnaphthalene (c) l-arnino-2-phenethyloxynaphthalene (d) 1-amino-2-phenoxynaphthalene (e) Z-arnino-1-methylmercaptonaphthalene (f) 1-amino-S-hexyloxynaphthalene (g) 1-arnino-3-benzylnaphthalene .(h) 1-amino-2-(trifiuoromethyl)naphthalene (i) 1-amino-2,4-dimethylnaphthalene (j) l-amino-8-bromonaphthalene I (k) Z-amino-6-tert-butylnaphthalene (l) 2-amino-3-bromo-5,6,7,S-tetrahydronaphthalene 1 (m) 1-amino-4-dimethylaminonaphthalene (n) 2-acetamido-6-aminonaphthalene there can be obtained respectively, accordingto this invention:

Following a procedure similar to that described in Example 17B and substituting for N-,(2-naphthyl)-2,2,4- trichlorobutyramide an equivalent amount of:

(a) N-(2-bromo-4,7-dinitro-1-naphthyl)-2,2,4-

trichlorobutyramide (b) N-(Z-methoxy-fi-methylsulfonyl-1-naphthy1)-2,2,4

trichlorobutyramide (c) N- (Z-phenethyloxyl-naphthyl -2,2,4-

trichlorobutyramide ,(d) N-(2-phenoxy-1-naphthyl)-2,2,4-

trichlorobutyramide (e) N-(1-methylmercapto-2-naphthyl)-2,2,4-

trichlorobutyramide (f) N-(S-hexyloxy-l-naphthyl)-2,2,4-

trichlorobutyramide (g) N- (3 -benzyl- 1 -naphthyl) -2,2,4-trichlorobutyramid (h) N- [2- (trifluoromethyl) -1naphthyl] -2,2,4-

trichlorobutyramide (i) N- (2,4-dimethyl-1-naphthyl) -2,2,4-

trichlorobutyramide (j) N-(8-bromo-1-naphthyl) -2,2,4-trichlorobutyrarnide (k) N-(6-tert-btuyl-2-naphthyl)-2,2,4-

trichlorobutyramide (l) N-(3-bromo-5,6,7,8-tetrahydro-2-naphthyl)-2,2,4

trichlorobutyramide (m) N- (4-dimethylamino-1-naphthyl) -2,2,4-

trichlorobutyramide (n) N- (2-acetamido-6-naphthyl -2,2,4 trichlorobutyramide there can be obtained respectively, according to this invention:

(a) 3,3-dichloro-l-(2-bromo-4,7-dinitr0-1-naphthyl)- 2-pyrrolidinone 17 ,(b) 3,3-dichloro-1-(2-methoxy-6-methylsulfonyl-1- naphthyl -2-pyrrolidinone (c) 3,3-dichloro-l(Z-phenethyloxy-1-naphthyl)-2- (l) 3,3-dichloro-1-(3-bromo-5,6,7,8-tetrahydro-2- naphthyl)-2-pyrrolidinone (m) 3,3-dichloro-1-,(4-dirnethylamino-1-naphthyl)-2- pyrrolidinone (n) 3,3-dichloro-1-(2-acetamido-6-naphthyl)-2- pyrrolidinone EXAMPLE 20 (A) N-(2,6-xylyl)-2,2,4-trichlorobutyramide To a stirred ice-cooled mixture of 6.06 g. 2,6-dimethylaniline in 100 ml. benzene and 5.62 g. sodium carbonate in 50 ml. water was added 10.5 g. 2,2,4-trichlorobutyryl chloride in 50 ml. benzene during one-half hour and stirring was continued one-half hour with cooling and one and one-half hours at room temperature. The benzene phase was separated, washed with dilute aqueous hydrochloric acid solution, water, dilute sodium bicarbonate solution and water, dried over calcium sulfate and evaporated to dryness to yield after recrystallization from hexane 12.8 g. N-(2,6-xylyl)-2,2,4-trichlorobutyramide; M.P. 119.0120.0 C.

(B) 3 ,3 -dichloro-1-(2,6-xylyl) -2-pyrrolidinone To 12.8 g. N-(2,6-xylyl)-2,2,4-trichlorobutyramide from Example 20A in 100 ml. ethyl alcohol was added, with stirring, a solution of 0.8 g. sodium hydroxide in ml. Water and when the pH of the reaction mixture returned to approximately seven an additional 0.8 g. sodium hydroxide in 10 ml. water was added. When the pH of the reaction mixture returned to approximately seven, it was adjusted to pH thirteen by the addition of 50% aqueous sodium hydroxide solution and stirring was continued for one hour. The reaction mixture was diluted with water and the resulting precipitate was collected by filtration and recrystallized from methyl alcohol-water to yield 8.7 g. 3,3-dichloro-1-(2,6-xylyl)-2-pyrrolidinone; M.P. 96.5-98.0 C.

EXAMPLE 21 (A) N-(2,4-difluorophenyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example A and using 6.46 g. 2,4-difluoroaniline, 5.62 g. sodium carbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained 13.6 g. N-(2,4-difluorophenyl)- 2,2,4-trichlorobutyramide as an oil which was used as such in the next step.

(B) 3,3-dichloro-1-(2,4-difluorophenyl)-2-pyrrolidinone Following a procedure similar to that described in Example 20B and using 13.6 g. N-(2,4-difluorophenyl)-2,2,4- trichlorobutyramide from Example 21A and 1.80 g. sodium hydroxide, there was obtained after recrystallization from methyl acetate-hexane 6.43 g. 3,3-dichloro-1-(2,4-difluorophenyl)-2-pyrrolidinone; M.P. 86-87" C.

18 EXAMPLE 22 (A) N- [3 phenoxy) phenyl] -2,2,4-trichlorob utyramide Following a procedure similar to that described in Example 20A and using 9.26 g. 3-phenoxyaniline, 5.62 g. sodium carbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained 16.4 g. N-[3-(phenoxy)phenyl]- 2,2,4-trichlorobutyramide as an oil which was used as such in the next step.

(B) 3,3-dichloro-1- [3- (phenoxy)phenyl] -2-pyrrolidinone Following a procedure similar to that described in EX- ample 20B and using 16.4 g. N-[3-(phenoxy)phenyl]'-2,2, 4-trichlorobutyramide from Example 22A and 3.83 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol-water 12.2 g. 3,3-dichloro-1-[3- (phenoxy)phenyl] -2-pyrrolidinone; M.P. 89.5-90.5 C.

EXAMPLE 23 (A) N- [4-chloro -2- (trifluoromethyl) phenyl] 2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 20A and using 9.78 g. 4-chloro-2-(trifluoromethyl)- aniline, 5.62 g. sodium carbonate, and 10.5 g. 2,2,4-trichlorobutyrylchloride, there was obtained N- [4-chloro-2- (trifiuoromethyl)phenyl] 2,2,4 trichlorobutyramide as crystals which were used as such in the next step.

(B) 3,3-dichloro-1-[4-chloro-2-(trifiuoromethyl)phenyl]- 2-pyrrolidinone Following a procedure similar to that described in EX- ample 20B and using the N-[4-chloro-2-(trifluoromethyl)- phenyl]-2,2,4-trichlorobutyramide from Example 23a and 2.0 g. sodium hydroxide, there was obtained after recrystallization from hexane 7.97 g. 3,3-dichloro-1-[4-chloro- 2-(trifluoromethyl)phenyl]-2-pyrrolidinone; M.P. 78- 80 C.

EXAMPLE 24 (A) N-[3,5-bis(trifluoromethyl)phenyl]-2,2,4- trichlorobutyramide Following a procedure similar to that described in Example 20A and using 11.5 g. 3,5-bis(trifiuoromethyDaniline, 5.62 g. sodium carbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained 19.9 g. N-[3,5-bis(trifluoromethyl)phenyl]-2,2,4-trichlorobutyramide as a solid which was used as such in the next step.

(B) 3,3-dichloro-1-[3,5-bis(trifluoromethyl) phenyl]- 2-pyrrolidinone Following a procedure similar to that described in Example 20B and using the N-[3,5-bis(trifluoromethyDphenyl]-2,2,4-trichlorobutyramide from Example 24A and 1.98 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol-water'8.19 g. 3,3-dichloro-1- [3,5 bis(trifiuoromethyl)phenyl] 2-pyrrolidinone; M.P. 88-90 C.

EXAMPLE 25 (A) N-(2,6-dimethyl-3-pyridyl)2,2,4- trichlorobutyramide To a stirred, ice-cooled mixture of 6.1 g. 3-amino-2,6- dimethylpyridine in ml. ethylene dichloride and 4.2 g. sodium bicarbonate in 50 ml. water was added 10.5 g. 2,2,4-trichlorobutyrylchloride in 25 ml. ethylene dichloride during one-half hour and stirring was continued onehalf hour. The ethylene dichloride phase was washed with dilute aqueous sodium bicarbonate solution and water and the ethylene dichloride layer was then extracted with one normal aqueous hydrochloric acid solution and water. The aqueous acidic solution was treated with aqueous sodium bicarbonate solution until neutral and the resulting oily precipitate was taken up in ether and the ethereal solution was dried over calcium sulfate and evaporated to dryness. The resulting oil, dissolved in acetone, was treated (B) 3,3-dichloro-1- (2,6-dimethyl-3-pyridyl) -2- pyrrolidinone To a stirred solution of 5 g. of the hydrochloride of N-(2,6-dimethyl 3 pyridyl) 2,2,4 trichlorobutyramide from Example 25A in 30 ml. ethyl alcohol was added a solution of 1.2 g. sodium hydroxide in 12 ml. water in small portions during twenty minutes and stirring was continued for one-half hour. The reaction solution was diluted with water and the resulting precipitate was collected by filtration and recrystallized from methyl-alcoholwater to yield 1.12 g. 3,3-dichloro-l-(2,6-dimethyl-3-pyridyl)-2-pyrrolidinone; M.P. 87.8-89.8 C. (corr.).

EXAMPLE 26 (A) N- 2-chloro-3 -pyridyl) -2,2,4-trichlorobutyramide A procedure was followed similar to that described in Example 25A using benzene instead of ethylene dichloride, 6.43 g. 3-amino-2-chloropyridine, 5.62 g. sodium carbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, except that the benzene phase was washed only with water and then evaporated to dryness to yield 14.8 g. N-(2-chloro-3-pyridyl)-2,2,4-trichlorobutyramide as crystals which were used as such in the next step.

(B) 3,3-dichloro-1- (2-chloro-3-pyridyl)-2-pyrro1idinone Following a procedure similar to that described in Example 25B and using 14.8 g. N-(2-chloro-3pyridyl)-2,2,4- trichlorobutyramide from Example 26A and 1.96 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol 8.1 g. 3,3-dichloro-l-(2-chloro-3- pyridyl)-2-pyrrolidin0ne; MJP. 128-130 C.

Following a procedure similar to that described in Example 25A and substituting for 3-amino-2,6-dimethylpyri dine an equivalent amount of:

(a) 2-aminopyridine (b) 3-aminopyridine (c) 4-aminopyridine (d) 5-amino-2-dimethylaminopyridine (e) 2-amino-6-hexylpyridine (f) 3-amino-6-ethoxy-2-methylmercaptopyridine (g) 3-amino-4ephenethylpyridine (h) S-amino-Z-benzyloxypyridine (i) 4-amino-2,4-dichloro-6-(trichloromethyl)pyridine (j) S-amino-Z-n-butylmercapto-3-nitropyridine (k) 3-amino-5-chloro-2-phenoxypyridine (l) Z-amino-5-tert-butylpyridine (m) 2-amino-3,5,6-trifluoropyridine n) S-amino-Z- (n-butylsulfonyl pyridine (o) 2-acetamido-6-aminopyridine there can be obtained respectively, according to this invention:

20 (m) N- 3,5 ,6-trifluoro-2-pyridy1) -2,2,4-trich10robutyramide (n) N-(2-n-buty1sulfony1-S-pyridyl)-2,2,4-trich1oro butyramide ,7 (o) N- (2-acetamido-6-pyridyl) -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 25B and substituting for N-(2,6-dimethyl-3-pyridyl)-2,2,4-trichlorobutyramide an equivalent amount of:

(a) N- Z-pyridyl -2,2,4-trichlorobutyramide (b) N-( 3 -pyridyl -2,2,4-trichlorobutyramide c) N- (4-pyridyl -2,2,4-trichlorobutyramide (d) N- (Z-dimethylamino-S-pyridyl) -2,2,4-trichlorobutyramide (e) N- 6-hexyl-2-pyridyl) -2,2,4-trichlorobutyramide (f) N 6-ethoxy-2-methylmercapto-3 -pyridy1) -2,2,4-

trichlorobutyramide (g) N- (4-phenethyl-3 -pyridyl) -2,2,4-trichlorobutyramide (h) N- 2-benzyloxy-5-pyridyl) -2,2,4-trichlorobutyramide (i) N- [2,3-dichloro-6- (trichloromethyl -4-pyridy1] 2,2,4-trichlorobutyramide (j) N- Z-n-butylmercapto-3 -nitro-5-pyridyl -2,2,4-

trichlorobutyramide (k) N- 5-chloro-2-phenoxy-3-pyridyl) -2,2,4-

trichlorobutyramide (l) N- S-tert-butyl-Z-pyridyl -2,2,4-trichlorobutyramide (m) N- 3,5 ,6-trifluoro-2-pyridyl -2,2,4-trichlorobutyramide (n) N- (2-n-butylsulfonyl-S-pyridyl) -2,2,4-trichlorobutyramide (o) N- 2-acetamido-6-pyridyl -2,2,4- (trichlorobutyramide there can be obtained respectively, according to this invention:

By treating 3,3-dichloro-1-(2-acetamido-6-pyridyl)-2- pyrrolidinone in absolute ethyl alcohol, at room temperature, with an ethereal solution containing an amount of hydrogen chloride slightly in excess of that required to hydrolyze the acetamido group, there can be obtained the dihydrochloride salt of 3,3-dichloro-1-(2-amino-6- pyridyl)-Z-pyrrolidinone which can be converted to the free base by dissolving the salt in ethyl alcohol .and treating the resulting solution with an equivalent of sodium carbonate in water.

EXAMPLE 27 (A) N-(S-chloro-Z-pyridyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described for Example 25A and using 11.9 g. Z-amino .5 i ehlo- 21 ropyridine, 6.42, g. sodium f carbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained 11.9 g. N-(5-chloro-2-pyridyl)-2,2,4-trichlorobutyramide as crystals which was used as such inthe next step.

(B) 3,3-dichloro-l-(5-chloro-2-pyridyl) -.2-pyrrolidinone Following a procedure similar to that described in Example 25B and using 11.9 g. N-(5-chloro-2-pyridyl)- 2,2,4-trichlorobutyramide from Example 27A and 1.58 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol 3.56 g. 3,3-dichloro-1-(5- chloro-2-pyridyl)-2-pyrrolidinone; M.P. 106-107" C.

EXAMPLE 2s (A) N-(4-chloro-2-benzothiazolyl)-2,2,4-trichlorobutyamide To a stirred ice-cooled mixture of 9.2 g. 2-amino-4- chlorobenzothiazole in 700 ml. ethylene dichloride and 5.63 g. sodium carbonate in 100 ml. water was added a solution of 10.5 g. 2,2,4-trichlorbutyryl chloride in 50 ml. ethylene dichloride dropwise during twenty minutes. Stirring was continued for two hours at room temperature and the ethylene dichloride phase was separated and washed with water, dried over sodium sulfate and evaporated to dryness to yield, after recrystallization from methyl alcohol-acetone-water, 13.6 g. N-(4-chloro-2-benzothiazolyl)-2,2,4-trichlorobutyramide; M.P. 150-l55 C.

' (B) 3,3-dichloro-1-(4-chloro-2-benzothiazolyl)-2- pyrrolidinone To a stirred solution of 13.6 g. N-(4-chloro-2-benzothiazolyl)-2,2,4-trichlorobutyramide from Example 28A in 400 ml. methyl alcohol at room temperature was added a solution of 1.53 g.sodium hydroxide in 10 ml. water dropwise. The pH of the mixture was adjusted to seven by the addition of 'a few drops 1 N aqueous hydrochloric acid solution and stirring was continued for five minutes. The mixture was diluted with 30 ml. water and the precipitate was collected by filtration and recrystallized from benzene-methyl alcohol to yield 9.36 g. 3,3-dichloro-1-(4- chloro-2-benzothiazolyl)-2-pyrrolidinone; M.P. 208-209 C.

Following a procedure similar to that described in Example 28A and substituting for 2-amino-4-chlorobenzothiazole an equivalent amount of:

(a) 2-aminobenzothiazole (b) 4-aminobenzothiazole (c) S-aminobenzothiazole '(d) 6 aminobenozthiazole (e) 7-aminobenzothiazole (f) 2-amino-6-n-butoxybenzothiazole (g) Z-amino-S,7-dichloro-4-methoxybenzothiazole (h) 2-aminc-6-ethylmercaptobenzothiazole (i) 6-amino-2-phenoxybenzothiazole (j) 6-amino-2-dimethylaminobenzothiazole (k) 2-amino-6-(trifluoromethyl)benzothiazole (l) 2-amino-4-bromo-6-methylsulfonylbenzothiaozle (rn) 5-amino-2-methyl-4-nitrobenzothiazole ,(n) 2-acetamido-6-aminobenzothiazole there can be obtained respectively, according to this invention:

(a) N-(2-benzothiazolyl)-2,2,4-trichlorobutyramide (b) N-(4-benzothiazolyl)-2,2,4-trichlorobutyramide (c) N-(S-benzothiazolyl)-2,2,4-trichlorobutyrarnide (d) N-(6-benzothiazolyl)-2,2,4-trichlorobutyramide (e) N-(7-benzothiazolyl)-2,2,4-trichlorobutyramide (f) N-(6-n-butoxy-2-benzothiazolyl)-2,2,4-trichlorobutyramide (g) N-(5,7-dichloro-4-methoxy-Z benzothiazolyl)-2,2,4-

trichlorobutyramide (h) N-(6-ethylmercapto-Z-benzothiazolyl)-2,2,4-

trichlorobutyramide (i) N-(Z-phenoxy-6-benzothiazolyl)-2,2,4-trichlorobutyramide (j) N- Z-dimethylarnino-6-benzothiazolyl -2,2,2-

trichlorobutyramide (k). N- 6- (trifiuoromethyl -2-benzothiazolyl] -2,2,4-

trichlorobutyramide (l) N- (4 bromo-6-methylsulfonyl-2-benzothiazolyl 2,2,4trichl0robutyramide (m) N-(2-methyl-4-nitro-5-benzothiazolyl)-2,2,4-

trichlorobutyramide (n) N- 2-acetamido-6-benzothiazolyl) -2,2,4-trichlorobutyramide.

Following a procedure similar to that described in Example 28B and substituting for N-(4-chloro-2-benzothiazolyl)-2,2,4-trichlorobutyramide an equivalent amount of:

, ga) N- Z-benzothiazolyl) -2,2,4-trichlorobutyramide (b) N-(4benzothiazolyl)-2,2,4-trichlorobutyramide (c) N-(S-benzothiazolyl)-2,2,4-trichlorobutyramide (d) N- 6-benzothiazolyl -2,2,4-trichlorobutyramide (e N- 7-benzothiazolyl -2,2,4-trichlorobutyrarnide (f) N-(6-n-butoxy-2-benzothiazolyl)-2,2,4-trichlorobutyramide (g) N-(5,7-dichloro-4-methoxy-2-benzothiazolyl)-2,2,4-

trichlorobutyramide (h) N-(6-ethylmercapto-2-benzothiazolyl)-2,2,4-

trichlorobutyramide (i) N- 2-phenoxy-6-benzothiazolyl -2,2,4-trichlorobutyramide (j) N-(Z-dimethylamino-6-benzothiazolyl) -2,2,4-

trichlorobutyramide (k) N- 6- (trifluoromethyl) -2-benzothiazolyl] -2,2,4-

trichlorobutyramide (l) N- 4-bromo-6-methylsulfonyl-2-benzothiazolyl 2,2,4-trichlorobutyramide (m) N-(2-methyl-4-nitro-5-benzothiazolyl)-2,2,4-

trichlorobutyramide (n) N-(2-acetamido-6-benzothiazolyl)-2,2,4-trichlorobutyramide there can be obtained respectively, according to this invention:

By treating 3,3-dichloro-1-(2-acetamido-G-benzothiazolyl)-2-pyrrolidinone in absolute ethyl alcohol, at room amount of hydrogen chloride slightly in excess of that required to hydrolyze the acetamido group, there can be obtained the hydrochloride salt of 3,3-dichloro-1-(2- amino-6-benzothiazolyl) 2 pyrolidinone which can be converted to the free base by dissolving the salt in ethyl alcohol and treating the resulting solution With an equivalent amount of sodium carbonate in water.

EXAMPLE 29' (A) N- (9-oxo-1-fiu0re nyl) -2,2,4-trichlr0butylramide To a stirred mixture of 5.65 g. 1-amino-9-fluorenone in 500 ml. ethylene dichloride and 3.83 g. sodium carbonate in 100 ml. water, at room temperature, was added a solution of 6.12 g. 2,2,4-trichlorobutyryl chloride in 50 ml. ethylene dichloride dropwise during twenty minutes. Stirring was continued for sixteen hours and the ethylene dichloride phase was separated and washed with water, dried over sodium sulfate, and evaporated to dryness to yield 10.5 g. N-(9-oxo-1-fiuorenyl)-2,2,4-trichlorobutyramide; M.P. 143-145 C.

(B) 3,3-dichloro-1-(9-oxo-1-fiuorenyl) -2-pyrrolidinone To a stirred solution of 9.5 g. N-(9-oxo-1-fluorenyl)- 2,2,4-trichlorobutyramide from Example 29A in 300 ml. methyl alcohol-methylene dichloride (prepared by dissolving the amide in 150 ml. refluxing methylene dichloride, adding 200 ml. methyl alcohol, and concentrating the resulting solution to 300 ml.), at room temperature, was added a solution of 1.0 g. sodium hydroxide in ml. water dropwise during five minutes. The reaction mixture was concentrated by evaporation to remove the methylene dichloride and diluted with water to yield after recrystallization from methylene dichloride-methanol 6.8 g. 3,3-dichloro-l-(9-oxo-1-fluorenyl)-2-pyrrolidinone; M.P. 160 161 C.

Following a procedure similar to that described in Example 29A and substituting for 1-amino-9-fiuorenone an equivalent amount of:

(a) l-aminofiuorene (b) Z-aminofiuorene (c) 3-arninofluorene (d) 4-aminofluorene (e) 3-amino-2-dimethylaminofiuoren-9-one (f) 2-amino-1,3-dibromo-7-nitrofluorene (g) 2-amino-7-methylsulfonylfluorene (h) l-amino-Z-methoxyfiuorene (i) 7-amino-3-methy1-2-nitrofiuoren-9-one (j) Z-amino-3-bromo-6,7-dichlorofluoren-9-one (k) 2-amino-7-benzylfluorene (l) Z-acetamido-3-aminofluorene there can be obtained respectively, according to this invention:

there can be obtained respectively, according to this h l invention (a) 3 ,3-dichloro-1-( l-fiuorenyl -2-pyrrolidinone (b) 3,3 -dichloro-1- (2-fluorenyl) -2-pyrrolidinone (c) 3 ,3-dichloro-1-(3-fluorenyl)-2-pyrrolidinone (d) 3 ,3-dichloro-1-(4-fiu0renyl) -2-pyrrolidinone iii 24 (e) 3,3-dichloro-1-(2-diethylamino-9-oxo-3-fluorenyl) 2- pyrrolidinone v (f) 3,3-dichloro-1-(1,3-dibromo-7-nitro-2-fluorenyl) 2 pyrrolidinone (g) 3,3-dichloro-1-(7-methylsulfonyl-2-fluorenyl)-2- pyrrolidinone I (h). 3,3-dichlor0-l-(Z-methoxy-l-fiuorenyl) 2-.

pyrrolidinone V p (i) 3,3-dichloro-1-(3-methyl-2-nitro-9-oxo-7 fluorenyl)- 2-pyrrolidinone (j) 3,3-dichl0ro-1-(3-bromo-6,7-dichloro-9-oxo-2- fiuorenyl)-2-pyrrolidinone (k) 3 ,3-dichloro-1-(7-benzy1-2-fluorenyl) -2-pyrrolidinone (l) 3,3-dichloro-1-(2-acetamido-3-fluorenyl)-2- I pyrrolidinone EXAMPLE 3 0 (A) N-(5,6,7,8-tetrahydro-l-naphthyl)-2,2,4-

trichlorobutyramide To a stirred ice-cooled solution of 7.35 g. 5,6,7,8-tetrahydro-l-naphthylamine in 250 ml. methylene dichloride and 5.6 g. triethylamine was added 11.6 g. 2,2,4-trichlorobutyryl chloride in 40 ml. methylene dichloride dropwise during fifteen minutes. The mixture Was diluted with chloroform and washed with dilute aqueous sodium bicarbonate solution and water. The organic phase was separated, dired over sodium sulfate and evaporated to dryness to yield 17.0 g. N-(5,6,7,8-tetrahydro-l-n'aphthyl)-2,2,4-trichlorobutyramide as a yellow oil which was used as such in the next step.

(B) 3,3-dichloro-1- 5,6,7,8-tetrahydrol-naphthyl -2- pyrrolidinone To a stirred ice-cooled solution of 16.0 g. N-(5,6,7,8- tetrahydro 1 naphthyl)-2,2,4-trichlorobutyramide from Example 30A in 150 ml. methyl alcoholwas-added a solution of Z'g. sodium hydroxide in 10 ml. water dropwise during five minutes. The reaction mixture was diluted with water and the precipitate was collected by filtration 'to yield after recrystallization from methylene dichloridehexane 9.2 g. 3,3-dichloro-1-(5,6,7,8-tetrahydr0-l-naphthyl)-2-pyrrolidinone; M.P. 129-131? C. 0

EXAMPLE 3 1 (A) N- 3,4-dichlorobenzyl -2,2,4-trichlorobutyramide To a stirred ice-cooled mixture of 17.6 g. 3,4-dichloro benzylamine in 200 ml. ethylene dichloride and 4.2 g. sodium hydroxide in 100 ml. water was added 21 g. 2,2,4- trichlorobutyryl chloride. The mixture was stirred for one-half hour and the precipitate was filtered'and washed with water. The ethylene dichloride layer was washed with dilute hydrochloric acid and water, dried over sodium sulfate, and evaporated to dryness to yield N-(3,4-dichl0- robenzyl)-2,2,4-trichlorobutyramide as a solid which 'was combined with the crop obtained by'filtration and used as such in the next step.

(B) 3,3-dichloro-1- (3,4-dichlorobenzyl) -2-pyrrolidinone (A) N-(4-chlorobenz yl)-2,2,4-trichlorobutyramide To a stirred ice-cooled mixture of 7.08 g. 4-chlorobenzylamine in ml. ethylene dichloride and 4.4 g. sodium bicarbonate in 50 ml. water, in a nitrogen atmosphere, was added a solution of 2,2,4-trichlorobutyryl chlo- 25 ride in 25 ml. ethylene dichloride dropwise duringonehalf hour and stirring was continued one-half hour. The ethylene dichloride phase was separated, washed,with dilute hydrochloric acid and water, and evaporated to dryness to yield N-(4-chlorobenzyl) 2,2,4-trichlorobutyramide which was used as such in the next step,

(B) 3,3-dichloro-l-(4-chlorobenzyl)-2-pyrrolidinone 1 To a stirred solution of the N-(4-chlorobenzyl)-2,2,4- trichlorobutyramide from Example 32A in 100 ml. ethyl alcohol, in a nitrogen atmosphere, was added a solution of 2.1 g. sodium hydroxide inwater dropwise during onehalf hour and stirring was continued one-half hour. The precipitate was filtered to give, after recrystallization from methyl alcohol-water 8.2 g. 3,3-dichloro-1-(4-chloro- 'benzyl)-2-pyrrolidinone, M.P. 7274 C.

Following a procedure similar to that described in Example 32A and substituting for 4-chlorobenzylamine an equivalent amount of (a) S-phenylhexylamine (b) 6-phenylhexylamine (c) 3-(3,4-dichlorophenyl)propylamine (d) benzylamine a (e) 4-benzylbenzylamine (f) 4-benzyloxybenzylamine (g) 4-n-butoxy-m-methyl'benzylamine (h) 2-chloro-3-rnethoxy-6-methylbenzylamine (i) 2-chloro4-rnethylsulfonylbenzylarnine (j) 2-chloro-6-nitrobenzylamine (k) a-methyl-4-phenoxybenzylamine (l) 3,4,S-trimethoxybenzylamine (m) 2-rnethylmercaptobenzylamine (n) 3-(trifiuoromethyl)benzylamine.

(o) 4-dimethylaminophenethylamine there can be obtained respectively, according to this invention:

(a) N- S-phenylhexyl -2,2,4-trichloro'butyramide (b) N-(6-phenylhexyl)-2,2,4-trichlorobutyramide (c) N-[3-(3,4-dichlorophenyl)propyl]-2,2,4-trichlorobutyramide (d) N-benzyl-2,2,4-trichlorobutyramide (e) N-(4-benzylbenzyl)-2,2,4-trichlorobutyramide (f) N-(4-benzyloxybenzyl)-2,2,4-trichlorobutyramide (g) N-(4-n-butoxy-a-methylbenzyl)-2,2,4-trichlorobutyramide (h) N-(2-chloro-3-methoxy-6-methylbenzyl)-2,2,4-trichlorobutyramide I j (i) N-(2-chloro-4-methylsulfonylbenzyl)-2,2,4-trichlorobutyramide (j N- (2-chloro-6-nitrobenzyl -2,2,4-trichlorobutyramide (k) N-.(a-methyl-4-phenoxybenzyl)-2,2,4-trichloro- .tyramide (l) N-(3,4,5-trimethoxybenzyl)-2,2,4-trichlorobutyramide (in) N-(Z-methylmercaptobenzyl)-2,2,4-trichlorobutyramide (n) N- 3- (trifluoromethyl) benzyl] -2,2,4-trichloro- .butyramide (o) N-(4-dimethylaminophenethyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 32B and substituting for N-(4-chlorobenzyl)-2,2,4- trichlorobutyramide an equivalent amount of:

(a) N-(5-phenylhexyl)-2,2,4-trichlorobutyramide (b) N-(6-phenylhexyl)-2,2,4-trichlorobutyramide ,(c) N-[3-(3,4-dichlorophenyl)propyl]-2,2,4-trichlorobutyramide (d) N-benZyl-Z,2,4-trichlorobutyramide (e) N-(4-benzylbenzyl)-2,2,4-trichlorobutyramide (f) N- (4-benzyloxybenzyl) -2,2,4-trichlorobutyramide i (g) N-(4-n-butoxy-a-methylbenzyl)-2,2,4-trichlorobutyramide 7 1 (h). N-(2-chloro-3-methoxy-6-methylbenzyl)-2,2 ,4-trichlorobutyramide (i) N-(2-chloro-4-meLhylsulfonylbenzyl)-2,2,4-trichlorobutyramide (j) N-(2-chloro6-nitrobenzyl) -2,2,4-trichlorobutyr amide (k) N-(a-methyl-4phenoxybenzyl)-2,2,4-trichlorobutyramide (l) N-(3,4,5-trimethoxybenzyl)-2,2,4-trichlorobutyramide a (m) N-(2-methylmercaptobenzyl)-2,2,4-trichlorobutyramide I Y (n) N-[3-(trifluoromethyl)benzyl]-2,2,4-trichlorobutyramide (o) N-(4-dimethylaminophenethyl)-2,2,4-trichlorou butyramide there can be obtained respectively, according to this invention:

(A) N- (4-chlorophenethyl) -2,2,4-trichlorobutyramide Following a procedure similar to that described in EX- ample 32A and using 7.78 g. 2-(4-chlorophenyl)ethylamine, 4.4 g. sodium bicarbonate, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-(4-chlorophenethyl)-2,2,4-trichlorobutyramide which was used as such in the next step.

(B 3,3-dichloro-1- (4-chlorophenethyl)-2-pyrrolidinone Following a procedure similar to that described in Example 32B and using the N-(4-chlorophenethyl)-2,2,4trichlorobutyramine from Example 33A, there was obtained after recrystallization from methyl alcohol 6.3 g. 3,3-dichloro-1-(4-chlorophenethyl)-2-pyrrolidinone; M.P. 78- 80 C.

EXAMPLE 34 (A) N-phenethyl-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 32A and using 6.05 g. phenethylamine, 2.1 g. sodium hydroxide, and 10.5 g. 2,2,4-trichlorobutyryl chloride, there was obtained N-phenethyl-2,2,4-trichlorobutyramide as an orange oil which was used as such in the next step.

(B) 3,3-dichloro-1-phenethyl-2-pyrrolidinone Following a procedure similar to that described .in Example 32-B and using, the N-phenethyl-2,2,4-trichlorobutyramide from Example 34A and 2.1 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol-water 7.9 g. 3,3 4 dichlor'o-l-phenethyl 2 pyrrolidinone, 84-85 C, f

EXAMPLE 35 i (A) N- 3- 3'-ind'olyl) propyl] -2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 32A and using 6.8 g. 3-(3-indolyl)propylamine,- 3.5 g. sodium bicarbonate, and 8.2 g;1,2,2,4-trichlorobutyryl chloride, there was obtained 12.5 g. -N-[3-(3-indolyl) propyl]-2,2,4-trichlorobutyramide-as a brown gum which was used as such in the next step.

(B) 3,3-dichlorol- 3 3-indolyl propyl] -2-pyrrolidinone Following a procedure similar to that described in Example 32B and using 12.5 g. N[3-(3-indolyl)propyl]- 2,2,4-trichlorobutyramide from Example 35A and 1.6 g. sodium hydroxide there was obtained after recrystallization from methyl alcohol 4.2 g. 3,3-dichloro-l-[3-(3-indolyl)propyl]-2-pyrrolidinone; M.P. l03l05 C.

Following a procedure similar to that described in Example 32A and substituting for 4-chlorobenzylamine an equivalent amount of:

there can be obtained respectively, according to this invention:

(a) N- 3-indolylmethyl -2,2,4-trichlorobutyramide (b) N- 2- 3-indolyl ethyl] -2,2,4-trichlorobutyramide (c) N- [2-(4-fluoro-3-indolyl)-2-methylethyl] 2,2,4-

trichlorobutyramide (d) N-[2-(5-methoxy-3-indolyl) -1-methylethyl] -2,2,4-

. trichlorobutyramide (e) N- [2- 5-benzyloxy-2-methyl-3-indolyl) ethyl] -2,2,4-

trichlorobutyramide (f) N- [2- (4,7-dichloro-3-indolyl) ethyl] -2,2,4-

trichlorobutyramide (g) N- [2- 5 -methylmercapto-3-indolyl ethyl] -2,2,4-

trichlorobutyramide (h) N -{2- [7- (trifluoromethyl -3-indolyl] ethyl}-2,2,4-

trichlorobutyramide (i) N [2- (5 -phenoxy-3indolyl ethyl] -2,2,4-

trichlorobutyramide (j) N- [2- 6-dimethylamino-3-indolyl ethyl] -2,2,4-

trichlorobutyramide (k) CN- [2- 4,5 ,6-trimethoxy-3-indolyl) ethyl] -2,2.4-

trichlorobutyramide (l) N- [2- 2-phenethyl-3-indolyl) ethyl] -2,2,4-

trichlorobutyramide (m) N- [2- 5-n-butoxy-3 -indolyl) ethyl]-2,2,4-

trichlorobutyramide Following a procedure similar to that described in Example 32B. and substituting for N-(4-chlorobenzyl)-2,2,4-

trichlorobutyramide an equivalent amount of:

(a) N- 3-indolylmethyl) -2,2,4-trichlorobutyramide (b) -N-[2-(3-indolyl)ethyl]-2,2,4-trichlorobutyramide (c) N- 2- (4-fluoro-3-indolyl Z-methylethyl] -2,2 ,4

trichlorobutyramide' (d) N- [2-(5methoxy-3indolyl)- l-methylethyl] -2,2,4

trichlorobutyramide 28 (e) N-[Z-(5 benzyloxy-2-methyl-3-indolyl)ethyl]r2,2,4- "trichlorob'utyramide, (f N-[Z- (4,7-dicl1loro-3 -indolyl) ethyl]-2,2,4-

trichlorobutyramide v (g) N [2(5-methylmercapto-3-indolyl)ethyl]-2,2,41

trichlorobutyramide (h) N -{2- [7'- (trifluoromethyl) -3-indolyl]'ethyl}-2,2,4

trichlorobutyramide p i) I N- 2- (.5-phenoxy-3-indolyl) ethyl] -2,2,4-

. trichlorobutyramide (j) N-[2-(6-dimethylamino-3-indolyl-)ethyl] 2,2,4-trichlorobutyramide 1 (k) N- [2- (4,5 ,6-trimethoxy-3 -indolyl) ethyl] 2,2,4-trichlorobutyramide (l) N- [2- 2-phenethy1-3 -indolyl-) ethyl] 2,2,4-trichlorobutyramide (m) N-[2-(5-n-butoxyr3-indolyl) ethyl] 2,2,4-trichlorobutyramide there can be obtained respectively, according to-this invention:

2-pyrrolidinone EXAMPLE 36 (A) N,N'-hexamethylene-bis(2,2,4 trichlorobutyramide .7

To a stirred ice-cooled mixture of 11.0 g. hexamethylenediamine in 200 ml. ethylene dichloride and 8.5 g. sodium hydroxide in 100 ml. water was added 42.0 g. 2,2,4- trichlorobutyryl chloride dropwise during one-half hour and stirring was then continued at room temperature for two hours. The mixture was diluted with water, washed with saturated aqueous sodium bicarbonate solution, water, dilute aqueous hydrochloric acid solution, and saturated sodium chloride solution. The ethylene dichloride phase was separated, dried'over magnesium sulfate, and evaporated to dryness to give on crystallization from hexane-ether 39.1 g. N,N'-hexamethylene-bis(2,2,4-trichloro butyramide); M.P. 8182 C.

(B) 1,1'-hexamethylene-bis(3,3 dichloro- 2-pyrrolidinone) To a solution of 10.0 g. N,N'-hexamethylene-bis(2,2,4- trichlorobutyramide) from Example 36A in 35 ml. dimethylsulfoxide was added 2.2 g of a mixture of sodium hydride in mineral oil (529% sodium hydride) and the mixture was stirred for one hour with occasional cooling in order to maintain the'reaction at' room temperature. The resulting"solution was heated on a steam bath until the pH reached seven and was then poured onto ice and extracted with chloroform. The chloroform solution was evaporated to dryness to yield atter recrystallization from 29 carbon tetrachlororide 4.1 g. 1,1'-hexamethylene-bis(3,3- diehloro-Z-pyrrolidinone); M.P. 90.6-91..8 C. (corn).

Following a procedure similar to that described in Example 36A and substituting for hexamethylenediamine an equivalent amount of: i

(a) ethylenediamine (b) octamethylenediamine (c) dodecamethylenediamine I (d) 1,2-diamino-2-methylpropane therecanbe obtained respectively, according to this invention:

(a) N,N-ethylene-bis(2,2,4-trichlorobutyramide) (b) N,N'-octamethylene-bis(2,2,4-trichlorobutyramide) (c) N,N'-dodecamethylene-bis(2,2,4-trichlorobutyramide) (d) N,N-(1,l-dimethylethylene)-bis(2,2,4-trichlorobutyramide) Following a procedure similar to that described in Example 36A and substituting for 2,2,4-trichlorobutyry1 chloride an equivalent amount of:

(a) 4chlorobutyryl chloride (b) S-chlorovaleryl chloride (c) 6-chlorohexanoy1 chloride there can be obtained respectively:

(a) N,N'-hexamethylene-bis(4-chlorobutyramide) (b) N,N-hexamethylene-bis(4-chlorovaleramide) (c) N,N'-hexamethylene-bis(-chlorohexanamide) Following a procedure similar to that described in Example 36B and substituting for N,N-hexamethylenebis(2,2,4-trichlorobntylramide) an equivalent amount of:

(a) N,N'-ethylene-bis(2,2,4-trichlorobutyramide) (b) N,N'-octamethylene-bis(2,2,4-trichlorobutyramide) (c) N,N'-dodecamethy1ene-bis(2,2,4-trichlorobutyramide) (d) N,N-( 1, l-dimethylethylene)-bis(2,2,4-trich10rm butyramide) (e) N,N'-hexamethylene-bis(4-chlorobutyramide) (f) N,N'-hexamethylene-bis(S-chlorovaleramide) (g) N,N'-hexamethylene-bis(6-chlorohexanamide) there can be obtained respectively, according to this invention:

(a) 1,1'-ethylene-bis(3,3-dichloro-Z-pyrrolidinone) (b) 1,1'-octamethylene-bis(3,3-dichloro-2-pyrrolidinone) (c) 1,1'-dodecamethylene-bis(3,3-dichloro- 2-pyrrolidinone) (d) 1,1'-(1,1-dimethylethylene)-bis(3,3-dichloro- 2-pyrrolidinone) (e) l,l'-hexamethylene-bis(2-pyrrolidinone) (f) 1,1'-hexamethylene-bis(2-piperidone) (g) 1,l'-hexamethylene-bis(hexahydro- 2H-azepin-2-one) Following the general procedure hereinbefore described for the chlorination of a 2-oxopolymethylenimine and using the following: o

(a) 1,1-hexamethylene-bis(2-pyrrolidinone) (b) 1,1'-heXamethylene-bis(2-piperidone) (c) 1,1'-hexamethylene-bis (hexahydro-2H-azepin 2-one) there can be obtained respectively:

(a) 1,1-hexamethylene-bis(3,3-dichloro-2-pyrrolidinone) (b) 1,1-hexamethylene-bis 3 ,3-dichloro-2-pipcridone) (c) 1,1'-hexamethylene-bis(3,3-dichlorohexahydro-2H- azipin-Z-one) EXAMPLE 37 (A) N,N'-(4-xylylene)bis(2,2,4-trichlorobutyramide) To a stirred, ice-cooled mixture of 6.8 g. 4,-xylylenediamine in 200 m1. ethylene dichloride and 4.2 g. sodium hydroxidein ml. water was added 21 g. of 2,2,4-trichlorobutyryl chloride dropwise during fifteen minutes and stirring was continued for one-half hour. The resulting precipitate Was collected by filtration and washed with water. The filtrate was washed with dilute aqueous hydrochloric acid solution and water, dried over sodium sulfate, and evaporated to dryness to yield, after combination with the crop obtained by filtration followed by trituration in ether-hexane, N,N-(4-xylylene)bis(2,2,4-trichlorobutyramide); M.P. 93-98 C.

(B) 1, 1 (4-xylylene bis 3,3-dichloro-2-pyrrolidinone) To a stirred solution of the N,N'-(4-xylylene)bis(2,2,4- trichlorobutyramide), from Example 37A, in 200 ml. ethyl alcohol was added a solution of 4.2 g. sodium hydroxide in 42 ml. water. Stirring was continued for ten minutes and dilute aqueous hydrochloric acid solution was added until the solution turned acidic, followed by 300 ml. water. The resulting crystals were filtered to give after recrystallization from chloroformhexane 4.9 g. 1,1'-(4- xyly1ene)bis(3,3-dichloro 2 pyrrolidinone); M.P. 219.2- 222.0 C. (dec.) (corr.).

Following a procedure similar to that described in Example 37A and substituting for 4-xylylenediamine an equivalent amount of:

(a) 2-xylylenediamine (b) 3-xylylenediamine (c) 2,2'-(4-phenylene)bis(ethylamine) (d) 2,2-(3-phenylene)bis(ethylamine) (e) 2,2-(2-phenylene)bis(ethylamine) (f) 2,2-(2,5-dimethyl-4-phenylene)bis(ethylamine) (g) 5-tert-butyl-3-xylylenediamine (h) 2,4,6-trimethy1-3-xylylenediamine (i) 4-meth0xy-6-methyl-3-xylylenediamine (j) a,a-dimethyl-4-xylylenediamine (k) 2,5-dimethoxy-4-xylylenediamine (l) 2,2-(4-pheny1ene)bis(l-methylethylamine) there can be obtained respectively, according to this invention:

Following a procedure similar to that described in Example 37A and substituting for 2,2,4-trichlorobutyryl chloride an equivalent amount of:

(a) 4-chlorobutyry1 chloride (b) S-chlorovaleryl chloride (c) fi-chlorohexanoyl chloride there can be obtained respectively:

(a) N,N-(4-xylylcne)bis(4-chlorobutyramide) (b) N,N- (4-Xylylene)bis(5-chl0rova1eramide) (c) N,N-(4-xyly lene)bis(6-chlorohexanamide) Following a procedure similar to that described in Example 373 and substituting for N,N'- (4-xylylene)bis (2,2,4-trichlorobutyramide) an equivalent amount of:

(a) .N,N'- 2-xylylene bis 2,2,4-trichloorb'utyramide) (b N,N.- 3-xyly1ene bis 2,2,4-trichlorobutyramide) (c N,N- 2,2'- (4-phenylene bisethyl] bis 2,2,4-trichlorobutyramide) (d N,N- [2,2'- 3-phenylene bisethyl] bis( 2,2,4-

trichlorobutyramide) (e) N,N- [2,2- 2-phenylene bisethyl] bis 2,2,4-

trichlorobutyramide) (f N,N'- [2,2- 2,5 -dimethyl-4-phenylene) bisethyl bis 1 (2,2,4-trichlorobutyramide) (g) N,N'- 5-tert-butyl-3-xylylene bis 2,2,4-trichloro butyramide) (h) N,N- (2,4,6-trirnethyl-3-xylylene bis 2,2,4-trichlorobutyramide) (i) N,N'- 4-methoxy-6-methyl-3-xylylene bis (2,2,4-

trichlorobutyramide) (j) N,N- u,u'-dimethyl-4-xylylene) bis 2,2,4-trichlorobutyramide) (k) N,N- 2,5 -dimethoxy-4-Xylylene bis 2,2,4-trichlorobutyramide) l) N,N'- [2,2'- (4-phenylene bis( l-methylethyl) 1bis (2,2,4-trichlorobutyramide) m N,N'- (4-xylylene bis 4-chlorobutyramide) (n) N,N' 4-xy1ylene bis S-chlorovaleramide) (o) N,N- 4-xyly1ene bis 6-chlorohexanamide) there can be obtained respectively, according to this invention:

( a) 1, 1- (2-xyly1ene bis (3 ,3-dichloro-Z-pyrrolidinone) (b) 1,1'- (3-xylylene) bis (3,3-dichloro-2-pyrrolidinone (c) 1, l [2,2'- (4-phenylene bisethyl] bis 3,3-dichloro-2- pyrrolidinone) d) 1,1- [2,2- (3-phenylene)bisethyl] bis (3,3-dich1oro-2- pyrrolidinone) (e) 1, 1 [2,2- 2-pheny1ene bisethyl] bis 3,3-dichloro-2- pyrrolidinone) (f) 1, 1 [2,2'- 2,5-dimethyl-4-phenylene) bisethyl] bis (3 ,3-dich1oro-2-pyrrolidinone) (g) 1, 1 5-tert-butyl-3 -xylylene bis 3,3-dichloro-2- pyrrolidinone) (h) 1,1'- (2,4,6-trimethyl-3-xyly1ene) bis(3 ,3-dichloro- Z-pyrrolidinone) (i) 1, 1 (4-methoxy-6-methyl-3-Xylylene) bis 3 ,3-

dichloro-Z-pyrrolidinone) (j) 1, l a,u'-dimethyl-4-xy1ylene) bis( 3,3-dichloro-2- pyrrolidinone) (k) 1, 1 2,5 -dimethoxy-4-xy1ylene bis 3,3-dich1oro-2- pyrrolidinone) (l) 1, 1 2,2'- 4-phenylene bis( l-methylethyl bis 3,3-

dichloro-Z-pyrrolidinone) m) 1,1- (4-xyly1ene bis( 2-pyrrolidinone) (n) 1,1'- (4-xylylene bis 2-piperidone) (0) 1,1'- (4-xylylene) bis (hexahydro-2H-azepin-2-one) Following the general procedure hereinbefore described for the chloroination of a 2-oxopolymethylenimine and using the following:

(a) 1,1'-(4-xylylene)bis(2-pyrrolidinone) (b) 1 1 (4-xylylene (bis (Z-piperidone) (c) 1,1-(4-xylylene)bis(hexahydro-2H-azepin-2-one) there can be obtained respectively:

(a) 1, 1 4-xylylene) bis 3 ,3-dichloro-2-pyrrolidinone) (b) 1,1'1(4-xylylene)bis(3 ,3-dichloro-2-piperidone) (c) 1,1-(4-xylylene) bis(3,3-dichlorohexahydro-2H- azepin-Z-one) EXAMPLE 38 (A) N,N-(2-ch1oro-1,4-phenylene)bis(2,2,4- trichlo robutyramide) To a stirred, ice-cooled mixture of 6.02 g. Z-chloro- 1,4-pheny1enediarnine in 150 ml. benzene and 6.15 g.

sodium carbonate in ml.,water was added a solutio'n of 11.5 g. 2,2,4-trichlorobutyryl chloride in 301111. ben zene dropwise during twenty minutes and stirring was.

continued with cooling for fifteen minutes and at room temperature for one and one-half hours. The benzene from hexane 8.33 g. N,N-(2-chlor0-1,4-phenylene)bis- (2,2,4-trichlorobutyramide); M.P. 90.09l.5 C.

(B) 1, 1 2-chloro- 1 ,4-phenylene bis 3 ,3 -dichl0ro- 2-pyrrolidinone) To a stirred mixture of 9.77 g. N,N-(2-chloro-I,4- phenylene)bis(2,2,4-trichlorobutyramide) in 75 ml. ethyl alcohol was added 0.8 g. sodium hydroxide in 10 ml. water. When the pH of the mixture returned to seven another 0.8 g. sodium hydroxide in 10 ml. water was added and when the pH returned to seven it-was adjusted to approximately thirteen by the addition of 50% aqueous sodium hydroxide solution. The mixture was diluted with water and the precipitate was filtered and washed with water to yield after recrystallization from acetone-hexane 5.8 g. 1,1 (2 chloro-1,4-phenylene)bis(3,3-dichloro2- pyrrolidinone); M.P. 240-242 C. (dec.).

Following a procedure similar to that described in Ex.- ample 38A and substituting for 2-chloro-1,4 -phenylenediamine an equivalent amount of:

there can be obtained respectively, according to this invention (a) N,N-( l ,2-phenylene bis 2,2,4-trichlorobutyramide) (b) N,N'-( 1,3-phenylene bis 2,2,4-trichlorobutyramide) (c) N,N'- 1,4-phenylene bis 2,2,4-trichlorobutyrarnide) (d) N,N' [3,4-di(trifluoromethyl)-1,2-phenylene] bis 2,2,4-trichlorobutyramide) (e) N,N- (5-bromo3,4-dimethyl-1,2phenylene)bis 2,2,4-trichlorobutyramide) (f) N,N'-(3,6-di-n-butoxy-1,2-phenylene)bis (2,2,4-

trichlorobutyramide) (g) N,N- 4-n-butyl- 1 ,Z-phenylene bis (2,2,4-

trichlorobutyramide) (h) N,N- (4-tert-butyl- 1 ,2-phenylene bis (2,2,4-

trichlorobutyramide) (i) N,N- (4,5 -dich1oro- 1 ,2-phenylene bis 2,2,4

trichlorobutyramide) (j) N,N-(4,6-diethylsulfonyl-1,3-phenylene)bis(2,2,4-

trichlorobutyramide) (k) N,N-. (4,6-diethy1mercaptol ,3-phenylene) bis (2,2,4-

trichlorobutyramide) (l) N,N-(4,5-dimethoxy-1,3-phenylene)bis(2,2,4-

trichlorobutyramide) (m) N,N-(2,6-dinitro-4-methoxy-1,3-phenylene) bis (2,2,4-trichlorobutyramide) (n) N,N'- 2,5 -diethoxy- 1 ,4-pheny1ene) bis (2,2,4-

trichlorobutyramide) o) N,N-(2-chloro-6-methoxy-1,4-phenylene)bis(2,2,4-

triehlerobntyramide) Y I 33 By following a procedure similar to that described in Example 38A and substituting for 2,2,4-trichlo'robutyryl chloride an equivalent amount of Following a procedure similar to that described in Example 38B and substituting for N,N'-(2-chloro-l,4- phenylene)bis(2,2,4 trichlorobutyramide) an equivalent amount of:

(a) N,N-(l,2-phenylene)bis(2,2,4-trichlorobutyramide) (b) N,N'-(1,3-phenylene)bis(2,2,4-trichlorobutyramide) (c) N,N-(1,4-phenylene)bis(2,2,4-trichlorobutyramide) (d) N,N'-[3,4-di(trifluoromethyl)-1,2-phenylene]bis (2,2,4-trichlorobutyramide) (e) N,N'(5-boro-3,4-dimethyl-1,2-phenylene)bis(2,2,4-

trichlorobutyramide) (f) N,N'-(3,6-di-n-butoxy-1,2-phenylene)bis(2,2,4-

trichlorobutyramide) (g) N,N'-(4-n-butyl-1,2-phenylene)bis(2,2,4-trichlorobutyramide) (h) N,N'- (4-tert-butyl-1,2-phenylene)bis(2,2,4-trichlorobutyramide) (i) N,N'-(4,5-dichloro-1,2-phenylene)bis(2,2,4-

trichlorobutyramide) (j) N,N'-(4,6-diethylsulfonyl-1,3-phenylene)bis(2,2,4-

trichlorobutyramide) (k) N,N- (4,6-diethyl'mercapto-l ,3-phenylene )bis (2,2,4-

trichlorobutyramide) (l) N,N-(4,5-dimethxy-1,3-phenylene)bis(2,2,4-trichlorobutyramide) (m) N,N'-(2,6-dinitro-4-methoxy-1,3-phenylene) bis(2,2,4-trichlorobutyramide) (n) N,N'-(2,5-diethoxy-1,4-phenylene)bis(2,2,4-trichlorobutyramide) (o) N,N'-(2-chloro-6-methoxy-1,4-phenylene)bis(2,2,4-

trichlorobutyramide) (p) N,N'-(2-chloro-1,4-phenylene)bis(4-chlorobutyramide) (q) N,N -(2-chloro-1,4-phenylene)bis(S-chlorovaleramide) (r) N,N-(2-chloro-1,4-phenylene)bis(6-chlorohexanamide) there can be obtained respectively, according to this invention:

(l) 1,1'-(4,5-dimethoxy-1,3-phenylene)bis(3,3-dichloro- 2-pyrrolidinone) (m) 1,1-(2,6-dinitro-4-methoxy-1,3-phenylene)bis(3,3-

dichloro-Z-pyrrolidinone) (n) 1,1'(2,5-diethoxy-1,4-phenylene)bis(3,3-dichloro- 2-pyrrolidinone) (o) 1,1-(2-chloro-6-methoxy-1,4-phenylene)bis(3,3-

dichloro-Z-pyrrolidinone) (p) 1,1'-(2-chloro-1,4-phenylene)bis(2-pyrrolidinone) (q) 1,1'-(2-chloro-l,4-phenylene)bis(2-piperidone) (r) l,1-(2-chloro-1,4-phenylene)bis(hexahydro-ZH- azepin-2-one) Following the general procedure hereinbefore described for the chlorination of a 2-oxopolymethylenimine and using the following: (a) 1,1-(2-chloro-l,4-phenylene)bis(2-pyrrolidinone) (b) 1,1'-(2-chloro-1,4-phenylene)bis(Z-piperidone) (c) 1,1-(2-chlor0-1,4-phenylene)bis (hexahydro-ZH- azepin-Z-one) there can be obtained respectively:

(a) 1,l'-(2-chloro-1,4-phenylene)bis(3,3-dichloro-2- pyrrolidinone) (b) 1,1(2-chloro-1,4-phenylene)bis(3,3-dichloro-2- piperidone) (c) 1,1-(2-chloro-l,4-phenylene)bis(3,3-dichlorohexahydro-2H-azepin-2-one) EXAMPLE 39 (A) N,N'-(4-chloro-1,3-phenylene)bis (2,2,4- trichlorobutyramide) Following a procedure similar to that described in Example 38A and using 7.12 g. 4-chloro-1,3-phenylenediamine, 11.24 g. sodium carbonate, and 21.0 g. 2,2,4-trichlorobutyryl chloride, there was obtained after crystallization from hexane 20.7 g. N,N-(4-ch1oro-1,3-phenylene)bis(2,2,4-trichlorobutyramide); M.P. 90.592.0 C.

(A) N,N'-(4-chloro-1,2-phenylene)bis(2,2,4- trichlorobutylramide) Following a procedure similar to that described in Example 38A and using 7.13 g. 4-chloro-1,2-phenylenediamine, 5.62 g. sodium carbonate, and 21.0 g. 2.24-trichlorobutyryl chloride, there was obtained 19.0 g. N,N- (4-chloro-1,2-phenylene)bis(2,2,4-trichlorobutyramide) as crystals.

(B) 1,1'-(4-chloro-1,2-phenylene)bis(3,3-dichloro-2- pyrrolidinone) v Following a procedure similar to that described in Example 38B and using 11.8 g. N,N'-(4-chloro-1,2-phenyl ene)-bis(2,2,4-trichlorobutyramide) from Example 40A and 3.88 g. sodium hydroxide, there was obtained after recrystallization from methyl alcohol 8.22 g. 1,'1-(4- chloro-l,2-p-phenylene)bis-(3,3 dichloro 2 pyrrolidinone);M.P. 228229 C.

EXAMPLE 4i (A) N,N'-(3,3'-dichlorq-4,4'-biphenylylene)bis( 2,2,4-

trichlorobutyramide) I i To a stirred mixture of 6.33 g. 3,3'-dichloro-4,4f-biphen yldiamine in .200 ml. benzene and 5.62 sodium carbonate in 60 ml. water, cooled to 10 C., 'was added a solution of 1015 g. 2,2,4-trichlorobutyryl chloride in 50 ml. benzene dropwise during twenty minutes and stirring was continued twenty minutes at to C. and one and one-half hours at room temperature. The benzene phase was separated, washed with water, saturated aqueous sodium bicarbonate solution, water, 1 N aqueous hydrochloric acid solution and water, dried over calcium sulfate, and evapporated to dryness to yield N,N'-(3,3'-dichloro-4,4'-biphenylylene) bis(2,2,4-trichlorobutyramide) as a viscous oil which was used as such in the next step.

(B) l,1'-(3,3'-dichloro-4,4-biphenylylene)bis( 3,3- dichloro-Z-pyrrolidinone) To a stirred mixture of the N,N'-(3,3'-dichloro-4,4'- biphenylylene)bis(2,2,4 trichlorobutyramide) from Example 41A in 100 ml. ethyl alcohol was added a solution of 1.0 g. sodium hydroxide in ml. water and when the pH returned to seven another solution of 1.0 g. sodium hydroxide in 20 ml. 'water was added and finally the pH was adjusted to approximately thirteen by the addition of a few drops of 50% aqueous sodium hydroxide solution. The mixture was diluted with water and the resulting precipitate was filtered to yield after recrystallization successively from acetone and chloroform 5.07 g. 1,1-(3,3'- dichloro-4,4-biphenylene)bis( 3,3 dichloro 2 pyrrolidinone); M.P. 265-266 C. (edc.).

Following a procedure similar to that described in EX- ample 41A and substituting for 3,3-dichloro-4,4-biphenyldiarnine an equivalent amount of:

(a) 2,2-biphenyldiamine (-b) 2,3'-biphenyldiamine (c) 2,4'-biphenyldiamine (d) 3,3'-biphenyldiamine (e) 3,4'-biphenyldiamine (f) 4,4-biphenyldiamine (g) 3,3'-dihexyloxy-4,4' biphenyldiamine (h) 4,5'-dinitro-2,2-biphenyldiamine (i) 5-chloro-2,4-biphenyldiamine (j) 2,2,4,4',6,6 'hexamethyl-3,3 biphenyldiamine (k) 4,4-di(trifluoromethyl)-2,2-biphenyldiamine \(l) 2,5,6-tribromo-6-iodo-3,4'-biphenyldiamine (m) 4,4'-dimethylmercapto-3,3-biphenyldiamine (n) 2,2'-dichloro-5,5'-diethoxy-4,4'-biphenyldiamine (o) 3,3'-diethyl-4,4-biphenyldiamine (p) 3,3'-diphenethyloxy-4,4-biphenyldiamine (q) 3,3'-diphenoxy-4,4'-biphenyldiamine (r) 3-methylsulfonyl-4,4-biphenyldiamine (s) 3',5'-dibromo-4-nitro-2,4-'-biphenyldiamine there can be obtained respectively, according to this invention:

(a) N,N 2,2'-biphenylylene bis (2,2,4-trichlorobutyramide) (b) N,N'- (2,3 -biphenylylene bis (2,2,4-trichlorobutyramide) (c) N,N'- 2,4'-biphenylylene bis (2,2,4-trichlorobutyramide) (d) N,N'- 3,3 '-b iphenylylene bis (2,2,4-trichlorobutyramide) (e) N,N'- 3,4-biphenylylene bis (2,2,4-trichlorob-utyr- (f) N,N'-(4,4'-biphenylylene )b-is (2,2,4-trichlorobutyramide) (g) N,N'- 3,3'-dihexyloxy-4,4-biphenylylene bis 2,2,4-trichlorobutyramide) (h) N,N'- (4,5 -dinitro-2,2'-biphenylylene bis 2,2,4-

trichlorobutyramide) (i) N,N'- (5 -chloro-2,4'- biphenylylene bis 2,2,4-trichlorobutyramide) (j) N,N'- (2,2',4,4',6,6-hexamethyl3,3 '-biphenylene) bis-2,2,4-trichlorobutyramide) (k) N,N [4,4-di (trifluoromethyl) 2,2-biphenylylene) Y bis (2,2,4-trichlorobutyramide) (l) N,N- 2',5 ,6--tribromo-6-iodo-3 ,4-biphenylylene) bis (2,2,4-trichlorobutyrami e) 36 r I a (m) N,N'- (4,4'-dimethylmercapto-3 ,3 '-biphenylylene bis(2,2,4-trichlorobutyramide) V (n) N,N'-(2,2'-dichloro-5,5-diethoxy-4,4'-biphenylylene)bis-(2,2 ,4trichloro butyramide)j (o) N,N-(3,3-diethyl-4,4'-biphenylylene)bis(2,2,4-

trichlorobutyramide) (p) N,N- 3,3'-diphenethyloxy-4-,4-biphenylylene) bis(2,2,4-trichlorobutyramide) (q) N,N'-(3,3'-diphenoxy-4,4'-biphenylylene)bis(2,2,4-

trichlorobutyramide) (r) N,N'- 3-methylsulfonyl-4,4'-biphenylylene bis (2,2,4-trichlorobutyramide) (s) N,N'-(3,5-dibromo-4-nitro-2,4-biphe'nylylene) bis(2,2,4-trich1orobutyramide) Following a procedure similar to that described in Example 41A and substituting for 2,2,4-trichlorobutyryl chloride an equivalent amount of:

(a) 4-chlorobutyryl chloride (b) 5-chlorovaleryl chloride (c) 6-chlorohexanoyl chloride there can be obtained respectively (a) N,N'- 3 ,3'-dichloro-4,4'-biphenylylene bis (4- chlorobutyramide) (b) N,N-(3,3'-dichloro-4,4'-biphenylylene)bis(5- chlorovaleramide) (c) N,N'-( 3,3'-dichloro-4-,4-biphenylylene bis 6- chlorohexanamide) Following a procedure similar to that described in Example 41B and substituting for N,N'-(3,3'-dichloro- 4,4 biphenylene)bis(2,2,4 trichlorobutyramide) an equivalent amount of: I

(a) N,N'-(2,2-biphenylylene bis (2,2,4-tr-ichlorobutyramide) I (b) N,N'-(2,3'-biphenyly1ene) bis (2,2,4-trichlorobutyramide) (c) N,N'- 2,4'-biphenylylene bis (2,2,4-trichlorobutyramide) (d) N,N'-(3,3 -biphenylylene) bis (2,2,4-trichlorobutyramide) (e) N,N'- 3,4'-biphenylylene bis (2,2,4-trichlorobutyramide) (f) N,N'- (4,4'-biphenylylene bis (2,2,4-trichlorobutyramide) (g) N,N'- 3,3'-dihexyloxy-4,4'-biphenylylene) bis (2,2,4-trichlorobutyramide) (h) N,N- (4,5 '-dinitro-2,2-biph'enylylene bis 2,2,4-

trichlorobutyramide) (i) N,N'- (5 -chloro-2,4-biphenylylene bis (2,2,4-trichlorobutyramide (j) N,N'- 2,2',4,4,6,6'-hexamethyl-3,3 '-biphenylylene) bis (2,2,4-trichlorobutyramide) (k) N,N'- [4,4-di (trifluoromethyl -2,2-biphenylylene] bis (2,2,4-trichlorobutyramide) (1) N,N'- (2,5,6'-tribromo-6-iodo-3 ,4'-biphenylylene) bis 2,2,4-trichlorobutyramide) (m) N,N'- (4,4-dirnethylmercapto-3 ,3 -biphenylylene) bis 2,2,4-trichlorobutyramide) (n) N,N(2,2-dichloro-5,5-diethoxy-4,4'-biphenylylene bis- 2,2,4-trichlorobutyramide) (o) N,N'- 3,3'-diethy1 4,4'-biphenylylene bis (2,2,4-

trichlorobutyramide) (p) N,N'- 3,3'-diphenethyloxy-4,4'-biphenylylene) bis(2,2,4-trichlorobutyramide) (q) N,N'- 3,3'-diphenoxy-4,4'-biphenylylene bis (2,2,4-trichlorobutyramide) (r) N,N 3-methylsulfonyl-4,4'-biphenylylene) his 2,2,4-trichlorobutyrarnide) (s) N,N'- 3',5 '-dibromo-4-nitro-2,4-ibiphenylylene) bis (2,2,4-trichlorobutyrarnide) (t) N,N'- (3 ,3 -dichloro-4,4'-biphenylylene bis (4- chlorobutyramide) (u) N,N- 3 ,3'-dichloro-4,4-biphenyly1ene bis 5 chlorovaleramide) a 3 7 (v) N,N'- 3,3'-dichloro-4,4'-biphenylylene bis (6- chlorohexanamide) there can be obtained respectively, according to this invention:

(a) 1,l-(2,2'-biphenylylene)bis(3,3-dichloro-2- pyrrolidinone) (b) 1,1- (2,3 '-biphenylylene) bis (3,3-dichloro-2- pyrrolidinone (c) 1,1'- (2,4'-biphenylylene) bis (3,3 -dichloro-2- pyrrolidinone) (d) 1, l 3,3 -*biphenylylene) bis 3,3-dichloro-2- pyrrolidinone) (e) 1,1-(3,4'-biphenylylene)bis(3,3-dichloro-2- pyrrolidinone) (f) 1,l-(4,4-biphenylylene)bis(3,3-dichloro- 2-pyrrolidinone) (g) 1,1-(3,3'-dihexyloxy-4,4-biphenylylene) bis 3 ,3-dichloro-2-pyrrolidinone) (h) 1, 1 (4,5 -dinitro-2,2'-biphenylylene bis- (3,3-dichloro-2-pyrrolidinone) (i) l,l'-(5-chloro-2,4-biphenylylene)bis- (3,3-dichloro-2-pyrrolidinone) (i) 1,1'-(2,2,4,4,6,6-hexamethyl-3,3'-biphenylylene) bis 3 3-dichloro-Z-pyrrolidinone) (k) l,1-(4,4-di(trifluoromethyl)-2,2'-biphenylylene) bis (3 ,3-dichloro-2-pyrrolidinone) (l) 1,1-(2,5,6-tribromo-6-iodo-3,4-biphenylylene)bis- (3,3-dichloro-2-pyrrolidinone) (m) l,l-(4,4'-dimethylmercapto-3,3'-biphenylylene)bis- (3,3-dichloro-2-pyrrolidinone) (n) 1,1-(2,2-dichloro-5,5'-diethoxy-4,4-biphenylylene) bis 3 ,3-dichloro-2-pyrrolidinone) 1,1'-(3,3'-diethyl-4,4-biphenylylene)bis- 3 ,3 -dichloro-2-pyrrolidinone) (p) l,1-(3,3'-diphenethyloxy-4,4'-biphenylylene)bis- -(3,3-dichloro-2-pyrrolidinone) (q) 1,1'-(3,3'-diphenoxy-4,4-biphenylylene)bis- (3,3-dichloro-2-pyrrolidinone) (r) 1,1'-(3-methylsulfonyl-4,4'-biphenylene)bis- (3,3-dichloro-2-pyrrolidinone) (s) l,l'-(3',5'-dibromo-4-nitro2,4'biphenylylene)bis- (3,3-dichloro-2-pyrrolidinone) (t) 1,1-(3,3'-dichloro-4,4'-biphenylylene)bis- (2-pyrrolidinone) (u) 1,l-(3,3'-dichloro4,4'-bipher1ylylene)bis- (Z-piperidone) (v) 1,1-(3,3'-dichloro-4,4-biphenylylene)bis- (hexahydro-ZH-azepin-Z-one) Following the general procedure hereinbefore described for the chlorination of a 2-oxopolymethylenimine and using the following:

(a) 1,1-(3,3'-dichloro-4,4-biphenylylene)bis- (2-pyrrolidinone) (b) 1,l'-(3,3'-dichloro-4,4'-biphenylylene)bis- (2-piperidone) (c) 1,1-(3,3'-dichloro-4,4'-biphenylylene)bis- (hexahydro-ZH-azepin-Z-one) there can be obtained:

(a) 1,1'-(3,3'-dichloro-4,4'-biphenylylene)bis- (3,3-dichloro-Z-pyrrolidinone) (b) l,1-(3,3'-dichloro-4,4'-biphenylylene)bis- (3,3-dichloro-2-piperidone)' (c) 1,1'-(3,3-dichloro-4,4'-biphenylylene)bis- (3,3-dichlorohexahydro-2H-azepin-2-one) EXAMPLE 42 (A) N-(2,6-dimethyl-4-pyrimidyl)-2,2,4-

trichlorobutyramide To a stirred solution'of 15.0 g. 4-amino-2,6-dimethylpyrimidine in 500 ml. ethylene dichloride and 13.0 g. sodium carbonate in 100 ml. water, at room temperature, was added 26 g. 2,2,4-trichlorobutyryl chloride in 50 ml.

ethylene dichloride dropwise during forty-five minutes and stirring was continued for four and one-half hours. The ethylene dichloride layer was separated, washed with water, dried over sodium sulfate, and evaporated to dryness to yield 22 g. of N-(2,6-dimethyl-4-pyrimidyl)-2,2,4- trichlorobutyramide as a yellow oil which was used as such in the next step.

(B 3, 3 -dichlorol- (2,6-dimethyl-4-pyrimidyl)-2-pyrrolidinone To a stirred ice-cooled solution of 20 g. N-(2,6-dimethyl-4-pyrimidyl)-2,2,4-trichlorobutyramide, from Example 42A, in 200' ml. methyl alcohol was added a solution of 2.4 g. sodium hydroxide in 10 ml. water and stirring was continued for one hour. The mixture was evaporated to a small volume and extracted with ethylene dichloride. The extract was washed with Water, dried over sodium sulfate and evaporated to dryness to yield, after trituration with cold ether and recrystallization from methyl alcohol-water and ether-hexane, 5.98 g. 3,3-dichloro-l-(2,6 dimethyl 4 pyrimidyl)-2-pyrrolidinone; M.P. 99-100 C.

Following a procedure similar to that described in Example 42A and substituting for 4-amino-2,6-dimethylpyrimidine an equivalent amount of:

(a) Z-aminopyrimidine (b) 4-aminopyrimidine (c) S-aminopyrimidine (d) 4-amino-5-bromo-6-chloro-2-methylmercaptopyrimidine (e) 5-amino-2,4-bis(dimethylamino)pyrimidine (f) 4-amino-2-n-butyl-6-chloro-S-nitropyrimidine (g) 4-amino-6-(trifiuoromethyl)pyrimidine (h) Z-amino-5-benzyl-4-chloropyrimidine (i) 5-amino-2,4-diphenoxypyrimidine (j) 4-amino-2-ethylsulfonyl-S-methylpyrimidine (k) 2-amino-5-n-butoxypyrimidine (l) 5-amino-4-chloro-6-methoxy-2-methylpyrimidine (m) 4-amino-5-hexyl-2-propylpyrimidine (n) Z-acetamido-S-aminopyrimidine there can be obtained respectively, according to this invention:

(a) N-(2-pyrirnidyl)-2,2,4-trichlorobutyramide (b) N- l-pyrimidyl) -2,2,4-trichl0robutyramide (c) N-(S-pyrimidyl)-2,2,4-trichlorobutyramide (d) -N-(5-bromo-6-chloro-2-methylmercapto- 4-pyrimidyl) -2,2,4-trichlorobutyramide (e) N- [2,4-bis dimethylamino) S-pyrimidyl] 2,2,4-trichlorobutyramide (f) N-(2-n-butyl-6-chloro-S-nitro-4-pyrimidyl)- 2,2,4-trichlorobutyramide g) N- [-6- (trifluoromethyl -4-pyrimidyl] 2,2,4-trichlorobutyramide (h) N-(S-benzyl-4-chloro-2-pyrimidyl)- 2,2,4-trichlorobutyramide (i) N-(2,4-diphenoxy-5-pyrimidyl)- 2,2,4-trichlorobutyramide (i) N-(Z-ethylsulfonyl-S-methyl-4-pyrimidyl)- 2,2,4-trichlorobutyramide (k) N-(5-n-butoxy-2-pyrimidyl)-2,2,4-trichlorobutyramide (1) N-(4-chloro--methoxy-Z-methyl-S-pyrimidy1)- 2,2,4-trich1orobutyramide (m) N-(5-hexyl-2-propyl-4-pyrimidyl)-2,2,4-trichlorobutyramide (n) N-(Z-acetamido-S-pyrimidyl)-2,2,4-trichlorobutyramide Following a procedure similar to that described in Example 42B and substituting for N(2,6-dimethyl-4- pyrimidyl) 2,2,4 trichlorobutyramide an equivalent amount of:

(a) N-(2-pyrimidyl){2,2,4-trichlorobutyramide (b) N-(4-pyrimidyl)-2,2,4-trichlorobutyramide (c) -N- S-pyrimidyl) -2,2,4-trichlorobutyramide (d) N-( bromo-6-chloro-2-rnethylmercapto-4-pyrimidyl)-2,2,4 trichlorobutyramide (e) N-[2,4-bis(dimethylamino)-5-pyrimidyl]-2,2,4-

trichlorobutyramide (f) N-(2-n-butyl-6-chloro-5-nitro-4-pyrimidyl)-2,2,4-

trichlorobutyramide (g) N- 6- (trifluoromethyl -4-pyrimidyl] -2,2,4-trichlorobutyramide (h) N- S-benzyl-4-chloro-2-pyrimidyl -2,2,4-trichloro- .butyramide (i) N- 2,4-diphenoxy-5-pyrimidyl) -2,2,4-trichlorobutyramide (1 N-(2-ethylsulfonyl-5-methyl-4-pyrimidyl) -2,2,4-

trichlorobutyramide (k) N-(5-n-butoxy-2-pyrimidyl)-2,2, 4-trichlorobtuyramide l N-(4-chloro-6-methoxy-2-rnethyl-5-pyrin1idyl) -2,2,4-

trichlorobutyramide (m) N-(5-hexyl-2-propyl-4-pyrimidyl)-2,2,4-trichlorobutyramide (n) N- (Z-acetamido-S-pyrimidyl) -2,2,4-trichlorobutyramide there can be obtained respectively, according to this invention:

(a) 3 ,3-dichloro-1-(2-pyrimidyl) -2-pyrrolidinone (b) 3,3-dichlorol 4-py1'imidyl -2-pyrrolidinone (c) 3,3-dichloro-1- S-pyrimidyl) -2-pyrrolidinone (d) 3 ,3 -dichloro-1-(5-bromo-6-chloro-2-methylmercapto-4-pyrimidyl -2-pyrrolidinone (e) 3,3-dichloro-1- [2,4-bis (dimethylamino) -5-pyrimidyl] 2-pyrrolidinone (f) 3 ,3-dichloro-1- (2-n-butyl-6-chloro-5-nitro-4- pyrimidyl) -2-pyrrolidinone 3,3-dichloro-1- [6-(trifluoromethyl) -4-pyrimidyl] -2- pyrrolidinone (h) 3 ,3-dichloro-1-(5-benzyl-4-chloro-2-pyrimidyl) -2- pyrrolidinone (i) 3,3-dichloro-1-(2,4-diphenoxy-S-pyrimidyl) -2-pyrrolidinone (1) 3,3-dichloro-1-(2-ethylsulfonyl-5-methy1-4-pyrimidyl -2-pyrrolidinone (k) 3 ,3-dichloro- 1 5 -n-butoxy-2-pyrimidyl -2-pyrrolidinone (l) 3 ,3 -dichloro-1- (4-chloro-6-methoXy-2-methyl-5- pyrimidyl -2-pyrrolidinone (m) 3,3-dichloro- 1- 5 -hexyl-2-propyl-4-pyrimidyl) -2- pyrrolidinone (n) 3,3-dich1oro-1- (2-acetamido-5-pyrimidy1) -2-pyrrolidinone By treating 3,3-dichloro-l-(Z-acetamido-S-pyrimidyl)-2- pyrrolidinone in absolute ethyl alcohol, at room temperature, with an ethereal solution containinng an amount of hydrogen chloride slightly in excess of that required to hydrolyze the acetamido group, there can be obtained the hydrochloride salt of 3,3-dichlor0-1-(2-amino-5-pyrimidyl)-2-pyrrolidinone which can be converted to the free base by dissolving the salt in ethyl alcohol and treating the resulting solution with an equivalent amount of sodium carbonate in water.

EXAMPLE 43 (A) N-(4-chlorophenyl)-5-chlorovaleramide To a stirred ice-cooled solution of 51 g. 4-chloroaniline and 45.1 g. triethylamine in 1300 ml. dry methylene dichloride was added a solution of 68.8 g. S-chlorovaleryl chloride in 200 ml. dry methylene dichloride dropwise during one hour and stirring was continued one hour with cooling and one hour at room temperature. The resulting solution was washed with water, saturated aqueous sodium bicarbonate solution and Water, dried over anhydrous calcium sulfate and evaporated to dryness under reduced pressure to give after recrystallization from ethyl acetate 40 hexane 91.9 g. N-(4-chlorophenyl)-5-chlorovaleramide; M.P. 109.5-110 C.

(B) N- 4-chlorophenyl -2-piperidone To a solution of 24.6 g. N-(4-chlorophenyl)-5-chlorovaleramide in 250 ml. ethyl alcohol was added 40 ml. of an aqueous solution containing 4 g. sodium hydroxide as follows: initially 10 ml. of solution was added and when the reaction solution became neutral another 10 ml. of solution was added. Finally when the reaction solution again became neutral 20 ml. of solution was added, stirring was continued for three hours and the resulting mixture was filtered and the filtrate was evaporated to dry ess under reduced pressure. The residue was taken up in ether, the mixture was filtered and the filtrate was evaporated to dryness to give after recrystallization from hexane 18.6 g. N-(4-chlorophenyl)-2-piperidone; M.P. 69.5-70.5 C.

(C) 3,3-dichloro-N-(4-chlorophenyl)-2-piperidone To a stirred slurry of 31.24 g. phosphorus pentachloride in 100 ml. xylene at room temperature was added a solution of 10.48 g. N-(4-chlorophenyl)-2-piperidone in ml. xylene dropwise during twenty-five minutes. The mixture was slowly heated to 89 during forty-five minutes, heating was continued one-half hour, and the mixture was evaporated to dryness under reduced pressure and the residue was stirred with 400 ml. 10% aqueous sodium carbonate and ice. The resulting solid was collected by filtration to give after recrystallization from and charcoal treatment in methanol 8.05 g. 3,3-dichloro-N-(4-chlorophenyl)-2-piperidone; M.P. l45146.5 C.

EXAMPLE 44 (A) N-(4-fiuorophenyl)-5-chlorovaleramide Following a procedure similar to that described in Example 43A and using 11.11 g. 4-fluoroaniline and 12.65 g. triethylamine in 340 ml. dry methylene dichloride and 17.04 g. S-chlorovaleryl chloride in 220ml. dry methylene dichloride there was obtained after recrystallization from ethyl acetate-hexane 19.12 g. N-(4-fluorophenyl)-5-chloro'valeramide; M.P. 8l.583 C.

(B) N- 4-fiuorophenyl) -2-piperidone Following a procedure similar to that described in Example 43B and using 11.48 g. N-(4-fluorophenyl)-4- chlorovaleramide in ml. ethyl alcohol and 25 ml. of an aqueous solution containing 2 g. sodium hydroxide there was obtained after recrystallization from hexane 6.35 g. N-(fiuorophenyl)-2-piperidone; M.P. 102- 104 C.

(C) 3,3-dichloro-N-(4-fluorophenyl)-2-piperidone Following a procedure similar to that described in Example 43C and using 31.3 g. phosphorus pentachloride in 100 ml. xylene and 9.66 g. of N-(4-fiuorophenyl)-2- piperidone in ml. xylene there was obtained after recrystallization from methanol 7.04 g. 3,3-dichloro-N-(4- fiuorophenyl)-2-piperidone; M.P. 140.5l4l.5 C

EXAMPLE 45 (A) N- (4-bromophenyl) -5-chlorovaleramide Following a procedure similar to that described in Example 43A and using 8.6 g. 4-bromoaniline and 6.06 g. triethylamine in 300 ml. dry methylene dichloride and 8.52 g. S-chlorovaleryl chloride in ml. dry methylene dichloride there was obtained after recrystallization from ethyl acetate-hexane 11.65 g. N (4 bromophenyl)-5- chlorovaleramide; M.P. 100-101 C.

(B N-(4-bromophenyl) -2-piperidone Following a procedure similar to that described in Example 43B and using 14.53 g. N-(4-bromophenyl)-5 chlorovaleramide in ml. ethyl alcohol and 10 ml. of 

